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Prognostic impact of albuminuria in early-stage chronic kidney disease on cardiovascular outcomes: a cohort study.

Issue N/A Vol N/A Published on 2025-01-01 PMID 39837596 PMCID N/A
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Keywords: Cardiovascular diseases, Biomarkers, Cohort studies, Heart Failure, risk factors
DOI: https://doi.org/10.1136/heartjnl-2024-324988
Authors: Khadija Yaqoob In X Hafiz Naderi In X Ross J Thomson In X Dunja Aksentijevic In X Magnus T Jensen In X Patricia B Munroe In X Steffen E Petersen In X Nay Aung In X Muhammed Magdi Yaqoob In X
Abstract:

Background

The impact of early-stage chronic kidney disease (CKD) on cardiovascular outcomes, particularly when albuminuria is present, remains unclear. This study examined the associations between early CKD (stages 1 and 2) with and without albuminuria and the incidence of major adverse cardiovascular events (MACEs), heart failure (HF) and all-cause mortality.

Methods

A cohort of 456 015 participants from the UK Biobank was categorised by CKD stage using serum creatinine to calculate estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (≥3 mg/mmol) to define albuminuria. Multivariable Cox proportional hazard models were applied to evaluate the associations between CKD stages and cardiovascular outcomes. Additionally, left ventricular mass (LVM), an intermediate cardiovascular risk marker, was assessed in a subset of participants using cardiovascular MRI.

Results

Compared with normal kidney function, the risk of adverse outcomes increased progressively with advancing CKD stages, except for stage 2 CKD without albuminuria. Stage 2 CKD with albuminuria was associated with higher risks of MACE (HR 1.32, 95% CI 1.25 to 1.38), HF (HR 1.79, 95% CI 1.67 to 1.92) and all-cause mortality (HR 1.51, 95% CI 1.44 to 1.58), comparable to stage 3A CKD without albuminuria. The presence of albuminuria significantly interacted with the relationships between CKD stages and outcomes. No significant differences in indexed LVM were observed between early-stage CKD with albuminuria and normal renal function.

Conclusions

In early-stage CKD, albuminuria is independently associated with increased risks of MACE, HF and mortality. These findings support the use of albuminuria over eGFR decline alone for cardiovascular risk stratification in early CKD.
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Relationship between left ventricular shape and cardiovascular risk factors: comparison between the Multi-Ethnic Study of Atherosclerosis and UK Biobank.

Issue N/A Vol N/A Published on 2025-01-01 PMID 39819617 PMCID N/A
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Keywords: Cohort studies, Magnetic Resonance Imaging, risk factors
DOI: https://doi.org/10.1136/heartjnl-2024-324658
Authors: Avan Suinesiaputra In X Kathleen Gilbert In X Charlene Mauger In X David A Bluemke In X Colin O Wu In X Nay Aung In X Stefan Neubauer In X Stefan K Piechnik In X Steffen E Petersen In X Joao A C Lima In X Bharath Ambale Venkatesh In X Alistair Young In X
Abstract:

Background

Statistical shape atlases have been used in large-cohort studies to investigate relationships between heart shape and risk factors. The generalisability of these relationships between cohorts is unknown. The aims of this study were to compare left ventricular (LV) shapes in patients with differing cardiovascular risk factor profiles from two cohorts and to investigate whether LV shape scores generated with respect to a reference cohort can be directly used to study shape differences in another cohort.

Methods

Two cardiac MRI cohorts were included: 2106 participants (median age: 65 years, 54% women) from the Multi-Ethnic Study of Atherosclerosis (MESA) and 2960 participants (median age: 64 years, 52% women) from the UK Biobank (UKB) study. LV shape atlases were constructed from 3D LV models derived from expert-drawn contours from separate core labs. Atlases were considered generalisable for a risk factor if the area under the receiver operating characteristic curves (AUC) were not significantly different (p>0.05) between internal (within-cohort) and external (cross-cohort) cases.

Results

LV mass and volume indices were differed significantly between cohorts, even in age-matched and sex-matched cases without risk factors, partly reflecting different core lab analysis protocols. For the UKB atlas, internal and external discriminative performance were not significantly different for hypertension (AUC: 0.77 vs 0.76, p=0.37), diabetes (AUC: 0.79 vs 0.77, p=0.48), hypercholesterolaemia (AUC: 0.76 vs 0.79, p=0.38) and smoking (AUC: 0.69 vs 0.67, p=0.18). For the MESA atlas, diabetes (AUC: 0.79 vs 0.74, p=0.09) and hypercholesterolaemia (AUC: 0.75 vs 0.70, p=0.10) were not significantly different. Both atlases showed significant differences for obesity.

Conclusions

The MESA and UKB atlases demonstrated good generalisability for diabetes and hypercholesterolaemia, without requiring corrections for differences in mass and volume. Significant differences in obesity may be due to different relationships between obesity and heart shapes between cohorts.
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The role of multi-modality imaging for the assessment of left atrium and left atrial appendage. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Issue N/A Vol N/A Published on 2025-01-01 PMID 39812172 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jeaf014
Authors: Leyla Elif Sade In X Francesco Fluvio Faletra In X Gianluca Pontone In X Bernhard Lothar Marie Gerber In X Denisa Muraru In X Thor Edvardsen In X Bernard Cosyns In X Bogdan A Popescu In X Allan Klein In X Thomas H Marwick In X Matteo Cameli In X Muhamed Saric In X Liza Thomas In X Nina Ajmone Marsan In X Ricardo Fontes-Carvalho In X Tomaz Podlesnikar In X Marianna Fontana In X Andre La Gerche In X Steffen Erhard Petersen In X Sarah Moharem-Elgamal In X Marcio Sommer Bittencourt In X Mani A Vannan In X Michael Glikson In X Petr Peichl In X Hubert Cochet In X Ivan Stankovic In X Erwan Donal In X
Abstract: Structural, architectural, contractile or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodeling has become a cornerstone diagnostic and prognostic marker. The structure and the function of LA and left atrial appendage (LAA) which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation (AF), cardioembolism, heart failure and mitral valve diseases. Rational use of various imaging modalities is key to obtain the relevant clinical information. Accordingly, this clinical consensus document from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists and cardiac imagers for the best practice of imaging LA and LAA for the diagnosis, management and prognostication of the patients.
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Excited to share our new paper, 'The role of multi-modality imaging for the assessment of left atrium and left atrial appendage. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).', with Sade et al. Always a pleasure to work with such a great team:
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Hypertrophic cardiomyopathy management: a systematic review of the clinical practice guidelines and recommendations.

Issue N/A Vol N/A Published on 2025-01-01 PMID 39749832 PMCID N/A
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Keywords: hypertrophic cardiomyopathy, Systematic review, Risk stratification, Practice Guidelines, Cardiomyopathies
DOI: https://doi.org/10.1093/ehjqcco/qcae117
Authors: Mihir M Sanghvi In X Eamon Dhall In X C Anwar A Chahal In X Constantinos O'Mahony In X Saidi A Mohiddin In X Konstantinos Savvatis In X Fabrizio Ricci In X Patricia B Munroe In X Steffen E Petersen In X Nay Aung In X Mohammed Y Khanji In X
Abstract:

Aims

In light of recent advances in imaging techniques, molecular understanding and therapeutic options in hypertrophic cardiomyopathy (HCM), we performed a systematic review of current guidelines for the diagnosis and management of HCM in order to identify consensus and discrepant areas in the clinical practice guidelines.

Methods and results

We systematically reviewed the English language guidelines and recommendations for the management of HCM in adults. MEDLINE and EMBASE databases were searched for guidelines published in the last 10 years. Following a systematic search, three guidelines on the diagnosis and management of HCM were identified, all of which were robustly developed (AGREE rigour of development score ≥50%). These guidelines were authored by the major European (ESC; 2023), American (AHA/ACC/AMSSM/HRS/PACES/SCMR; 2024) and Japanese (JCS/JHFS; 2018) cardiovascular societies. There was broad consensus on echocardiographic recommendations, the medical and invasive management of HCM, the application of genetic testing and family screening, and exercise and reproductive recommendations in HCM. There were areas of variability in the definition and diagnostic criteria for HCM, cardiovascular magnetic resonance (CMR) imaging recommendations and assessment of sudden cardiac death (SCD) risk and prevention strategies. Due to the JCS/JHFS guideline being older, there are no recommendations on the use of cardiac myosin ATPase inhibitors.

Conclusion

Contemporary guidelines for HCM achieve consensus across a broad range of criteria and recommendations concerning diagnosis and management. However, variations in the approach towards risk assessment for SCD exist between the guidelines. There are also more subtle differences concerning diagnostic criteria and the utility of late gadolinium enhancement for risk stratification, which will likely evolve as the evidence-base broadens.
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Cardiovascular magnetic resonance in patients with mitral valve prolapse.

Issue 1 Vol 27 Published on 2024-12-01 PMID 39725235 PMCID N/A
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Keywords: Mitral regurgitation, Sudden Cardiac Death, Mitral Valve Prolapse
DOI: https://doi.org/10.1016/j.jocmr.2024.101137
Authors: Stefano Figliozzi In X Silvana Di Maio In X Georgios Georgiopoulos In X Bert Vandenberk In X Amedeo Chiribiri In X Marco Francone In X Nay Aung In X Steffen E Petersen In X Tim Leiner In X Jan Bogaert In X Pier-Giorgio Masci In X
Abstract: With a prevalence of 2-3% in the general population, mitral valve prolapse (MVP) is the most common valvular heart disease. The clinical course is benign in the majority of patients, although severe mitral regurgitation, heart failure, and sudden cardiac death affect a non-negligible subset of patients. Imaging of MVP was confined to echocardiography until a few years ago when it became apparent that cardiovascular magnetic resonance (CMR) could offer comparative advantages for detecting and quantifying mitral valve abnormalities alongside tissue myocardial characterization. The present review highlights the growing body of evidence supporting the role of CMR in patients with MVP. Based on the recent literature, CMR appears not as a simple alternative to echocardiography in patients with poor acoustic windows, but as a complementary imaging modality instrumental for better quantifying mitral valve abnormalities, mitral regurgitation severity, ventricular remodeling, and myocardial tissue changes. In this respect, pivotal CMR studies highlight that mitral annular disjunction and myocardial fibrosis by late gadolinium enhancement are associated with a heightened risk of life-threatening ventricular arrhythmias (arrhythmic MVP). We also delineate how these and other markers (e.g., the severity of mitral regurgitation) could enable a personalized risk assessment in patients with MVP and implement clinical decision-making. Here, we provide a comprehensive review of the current literature, with an emphasis on the arrhythmic MVP phenotype. The review also provides some practical suggestions on how to carry out a dedicated CMR protocol in MVP and composes a thorough report to inform clinicians on key aspects of this valvular heart disease.
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Our latest publication 'Cardiovascular magnetic resonance in patients with mitral valve prolapse.' offers novel methodological insights from Figliozzi et al:
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Leucocyte telomere length and conduction system ageing.

Issue N/A Vol N/A Published on 2024-12-01 PMID 39689933 PMCID N/A
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Keywords: Genetics, Electrophysiology, epidemiology
DOI: https://doi.org/10.1136/heartjnl-2024-324875
Authors: Stefan van Duijvenboden In X Christopher P Nelson In X Zahra Raisi-Estabragh In X Julia Ramirez In X Michele Orini In X Qingning Wang In X Nay Aung In X Veryan Codd In X Svetlana Stoma In X Elias Allara In X Angela M Wood In X Emanuele Di Angelantonio In X John Danesh In X Nicholas C Harvey In X Steffen E Petersen In X Patricia B Munroe In X Nilesh J Samani In X
Abstract:

Background

Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.

Methods

In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59 868 and 62 266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420 071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR).

Results

Mean PR interval and QRS duration were 144.2 ms (± 20.4) and 92.3 ms (± 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95% CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered.

Conclusions

Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age.
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The Restitution Threshold Index Characterizes the Association Between Atrial Fibrillation Ventricular Rate and Ejection Fraction.

Issue N/A Vol N/A Published on 2024-12-01 PMID 39665707 PMCID N/A
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Keywords: Heart rate, Atrial fibrillation, Catheter ablation, Holter Monitoring, Ventricular Dysfunction
DOI: https://doi.org/10.1016/j.jacep.2024.10.020
Authors: Nikhil Ahluwalia In X Shohreh Honarbakhsh In X Abhishek Joshi In X Hakam Abbass In X Anthony W Chow In X Mehul Dhinoja In X Steffen E Petersen In X Guy Lloyd In X Ross J Hunter In X Richard J Schilling In X
Abstract:

Background

Patients with reduced left ventricular ejection fraction (LVEF) and rate-controlled atrial fibrillation (AF) may improve after restoring sinus rhythm. This may be due to the elimination of the short R-R intervals during AF even when mean heart rate is acceptable.

Objectives

This work aims to evaluate a novel parameter representing the burden of short R-R intervals during AF and its association with reduced LVEF and LVEF recovery after catheter ablation (CA).

Methods

Patients with persistent AF were prospectively enrolled pre-CA and grouped as having reduced (LVEF ≤50%) or preserved LVEF. Sequential R-R intervals on resting Holter monitoring were measured. We sought to define a threshold R-R interval at which the difference in the percentage of short R-R intervals is greatest when comparing patients with reduced and preserved ejection fraction. We termed this threshold the restitution threshold (RT) in the belief that this may be possible to apply as a threshold to identify patients with AF-mediated cardiomyopathy. This percentage burden of intervals shorter than the RT was defined as the restitution threshold index (RTI). The association with reduced LVEF in AF and predicting improvement in LVEF after CA was then evaluated.

Results

One hundred four patients were enrolled; 53 (51%) had a reduced LVEF. There was no difference in mean heart rate; however, at an RT of 660 ms, the RTI was higher in the reduced LVEF arm (56.1% ± 23.1% vs 39.5% ± 26.0%; P < 0.001). It was an independent predictor of left ventricular systolic dysfunction. The RTI in the reduced LVEF arm had an area under the receiver operating characteristic of 0.74 (95% CI: 0.47-0.95) and positive predictive value of 0.97 for LVEF improvement after CA, which was observed in 39 of 47 (83.0%) participants in sinus rhythm.

Conclusions

The RTI in persistent AF was associated with a reduced LVEF, whereas mean heart rate was not. The RTI could be used to predict LVEF improvement after CA.
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Our latest publication 'The Restitution Threshold Index Characterizes the Association Between Atrial Fibrillation Ventricular Rate and Ejection Fraction.' offers novel methodological insights from Ahluwalia et al:
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Clinical features, myocardial injury and systolic impairment in acute myocarditis.

Open Access Issue 2 Vol 11 Published on 2024-12-01 PMID 39627021 PMCID PMC11624809
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Keywords: Diabetes mellitus, Biomarkers, Myocarditis, Magnetic Resonance Imaging
DOI: https://doi.org/10.1136/openhrt-2024-002901
Authors: Vijay Shyam-Sundar In X Greg Slabaugh In X Saidi A Mohiddin In X Steffen Erhard Petersen In X Nay Aung In X
Abstract:

Objective

Cardiovascular magnetic resonance (CMR) is increasingly used in the diagnosis of myocarditis, with myocardial injury and systolic dysfunction playing key roles in the prognosis of this clinical setting. The clinical determinants of myocardial injury and systolic impairment in acute myocarditis are poorly defined. The aim of the current study is to assess the association of laboratory markers, late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF) in patients with acute myocarditis.

Methods

We completed a retrospective cohort study from a tertiary referral centre in London with CMR and acute myocarditis. Cases with cardiomyopathy were excluded. Missing data was imputed for selected clinical variables. We evaluated the association between peak troponin and LGE extent and LVEF. We adjusted the models for age, sex and time to CMR with a sensitivity analysis adjusting for body mass index and cardiovascular risk factors including hypertension, dyslipidaemia, diabetes mellitus and smoking.

Results

127 patients had abnormal T2-weighted imaging/mapping results with 118 (93%) presenting with chest pain and/or shortness of breath. Left ventricular LGE was identified in 118 (93%) patients and LVEF was 58±11%. The median time from the peak troponin to CMR was 1 day (IQR 0-6 days). The highest tertile of peak troponin was associated with more LGE (incident rate ratio 1.33, 95% CI: 1.07 to 1.64) and a lower LVEF (coefficient -5.3%, 95% CI: -9.5% to -1.1%). Diabetes was also associated with more LGE (incident rate ratio 1.90, 95% CI: 1.37 to 2.61) and lower LVEF (coefficient -8.9%, 95% CI: -14.7% to -1.8%).

Conclusions

Peak troponin is associated with more LGE and a lower LVEF even after accounting for demographics and comorbidities. Myocardial injury and systolic dysfunction play key roles in prognosis and future work incorporating clinical features into a risk prediction model may enable better risk stratification in acute myocarditis.
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Development and comprehensive evaluation of a national DBCG consensus-based auto-segmentation model for lymph node levels in breast cancer radiotherapy.

Issue N/A Vol 201 Published on 2024-12-01 PMID 39374675 PMCID N/A
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Keywords: Breast cancer, Radiotherapy, National, Target Delineation, Quantitative And Qualitative Evaluation, Deep Learning-based Auto-segmentation
DOI: https://doi.org/10.1016/j.radonc.2024.110567
Authors: Emma Skarsø Buhl In X Ebbe Laugaard Lorenzen In X Lasse Refsgaard In X Anders Winther Mølby Nielsen In X Annette Torbøl Lund Brixen In X Else Maae In X Hanne Spangsberg Holm In X Joachim Schøler In X Linh My Hoang Thai In X Louise Wichmann Matthiessen In X Maja Vestmø Maraldo In X Mathias Maximiliano Nielsen In X Marianne Besserman Johansen In X Marie Louise Milo In X Marie Benzon Mogensen In X Mette Holck Nielsen In X Mette Møller In X Maja Sand In X Peter Schultz In X Sami Aziz-Jowad Al-Rawi In X Saskia Esser-Naumann In X Sophie Yammeni In X Stine Elleberg Petersen In X Birgitte Vrou Offersen In X Stine Sofia Korreman In X
Abstract:

Background and purpose

This study aimed at training and validating a multi-institutional deep learning (DL) auto segmentation model for nodal clinical target volume (CTVn) in high-risk breast cancer (BC) patients with both training and validation dataset created with multi-institutional participation, with the overall aim of national clinical implementation in Denmark.

Materials and methods

A gold standard (GS) dataset and a high-quality training dataset were created by 21 BC delineation experts from all radiotherapy centres in Denmark. The delineations were created according to ESTRO consensus delineation guidelines. Four models were trained: One per laterality and extension of CTVn internal mammary nodes. The DL models were tested quantitatively in their own test-set and in relation to interobserver variation (IOV) in the GS dataset with geometrical metrics, such as the Dice Similarity Coefficient (DSC). A blinded qualitative evaluation was conducted with a national board, presented to both DL and manual delineations.

Results

A median DSC > 0.7 was found for all, except the CTVn interpectoral node in one of the models. In the qualitative evaluation 'no corrections needed' were acquired for 297 (36 %) in the DL structures and 286 (34 %) for manual delineations. A higher rate of 'major corrections' and 'easier to start from scratch' was found in the manual delineations. The models performed within the IOV of an expert group, with two exceptions.

Conclusion

DL models were developed on a national consensus cohort and performed on par with the IOV between BC experts and had a comparable or higher clinical acceptance than expert manual delineations.
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Thrilled to see our study, 'Development and comprehensive evaluation of a national DBCG consensus-based auto-segmentation model for lymph node levels in breast cancer radiotherapy.', now published! Kudos to Buhl and the entire team for their hard work:
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How to conduct clinical research in cardiovascular imaging: a primer for clinical cardiologists and researchers-a statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.

Issue 1 Vol 26 Published on 2024-12-01 PMID 39226295 PMCID N/A
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Keywords: Research, research methodology, Study Design, Clinical Trials, Cardiovascular Imaging
DOI: https://doi.org/10.1093/ehjci/jeae238
Authors: Denisa Muraru In X Gianluca Pontone In X Ruxandra Jurcut In X Julien Magne In X Erwan Donal In X Ivan Stankovic In X Constantinos Anagnostopoulos In X Philipp E Bartko In X Bart Bijnens In X Marianna Fontana In X Elena Galli In X Blazej Michalski In X Martina Perazzolo Marra In X Théo Pezel In X Alexia Rossi In X Otto A Smiseth In X Nico Van de Veire In X Thor Edvardsen In X Steffen E Petersen In X Bernard Cosyns In X Daniele Andreini In X Philippe Bertrand In X Victoria Delgado In X Marc Dweck In X Kristina Haugaa In X Niall Keenan In X Thomas H Marwick In X Danilo Neglia In X
Abstract: This statement from the European Association of Cardiovascular Imaging (EACVI) of the ESC aims to address the fundamental principles that guide clinical research in the field of cardiovascular imaging. It provides clinical researchers, cardiology fellows, and PhD students with a condensed, updated, and practical reference document to support them in designing, implementing, and conducting imaging protocols for clinical trials. Although the present article cannot replace formal research training and mentoring, it is recommended reading for any professional interested in becoming acquainted with or participating in clinical trials involving cardiovascular imaging.
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Rigorous exploration in 'How to conduct clinical research in cardiovascular imaging: a primer for clinical cardiologists and researchers-a statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.'. Groundbreaking research by Muraru & team published:
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Management of acute myocarditis: a systematic review of clinical practice guidelines and recommendations.

Issue 8 Vol 10 Published on 2024-12-01 PMID 39179417 PMCID N/A
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Keywords: Myocarditis, Systematic review, immunosuppression, Cardiovascular Magnetic Resonance, Guideline Recommendations
DOI: https://doi.org/10.1093/ehjqcco/qcae069
Authors: Vijay Shyam-Sundar In X Adil Mahmood In X Greg Slabaugh In X Anwar Chahal In X Steffen E Petersen In X Nay Aung In X Saidi A Mohiddin In X Mohammed Y Khanji In X
Abstract: The management of acute myocarditis (AM) is addressed in multiple clinical guidelines. We systematically reviewed current guidelines developed by national and international medical organizations on the management of AM to aid clinical practice. Publications in MEDLINE, EMBASE and Cochrane were identified between 1 January 2013 and 12 April 2024. Additionally, the websites of relevant organizations and the Guidelines International Network, Guideline Central, and NHS knowledge and library hub were reviewed. Two reviewers independently screened titles and abstracts, two reviewers assessed the rigour of guideline development, and one reviewer extracted the recommendations. Two of the three guidelines identified showed good rigour of development. Those rigorously developed agreed on the definition of AM, sampling serum troponin as part of the workflow for AM, testing for B-type natriuretic peptides in heart failure, key diagnostic imaging in the form of cardiovascular magnetic resonance, coronary angiography to exclude significant coronary disease, indications for endomyocardial biopsy (EMB), and indications for immunosuppression and advanced treatment options. Discrepancies exist in sampling creatine kinase-myocardial bound as a marker of myocardial injury, indications for EMB, and indications for immunosuppression and treatment of uncomplicated AM. Evidence is lacking for the use of 18F-Fluorodeoxyglucose Positron Emission Tomography for myocardial imaging, exercise restriction, follow-up measures, and genetic testing, and there are few high-quality randomized trials to support treatment recommendations. Recommendations for management of AM in the guidelines have largely been developed from expert opinion rather than trial data.
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Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: Prognostic insights.

Open Access Issue 6 Vol 11 Published on 2024-12-01 PMID 39132877 PMCID PMC11631267
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Keywords: MRI, Cardiovascular Magnetic Resonance, Left Ventricular Filling Pressure, Heart Failure Epidemiology
DOI: https://doi.org/10.1002/ehf2.15011
Authors: Ross J Thomson In X Ciaran Grafton-Clarke In X Gareth Matthews In X Peter P Swoboda In X Andrew J Swift In X Alejandro Frangi In X Steffen E Petersen In X Nay Aung In X Pankaj Garg In X
Abstract:

Background

Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non-invasively. At the population level, the prognostic role of CMR-modelled PCWP remains unknown. Furthermore, the relationship between CMR-modelled PCWP and established risk factors for cardiovascular disease has not been well characterized.

Objective

The main aim of this study was to investigate the prognostic value of CMR-modelled PCWP at the population level.

Methods

Employing data from the imaging substudy of the UK Biobank, a very large prospective population-based cohort study, CMR-modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR-modelled PCWP (≥15 mmHg). Cox regression was used to examine the impact of typical risk factors and CMR-modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE).

Results

Data from 39 163 participants were included in the study. Median age of all participants was 64 years (inter-quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR-modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44-1.70, P < 0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52-1.62, per standard deviation (SD) increment, P < 0.001], male sex (OR 1.37, 95% CI 1.26-1.47, P < 0.001), age (OR 1.33, 95% CI 1.27-1.41, per decade increment, P < 0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02-1.19, P = 0.012). After adjusting for potential confounders, CMR-modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07-4.07, P < 0.001] and MACE (HR 1.48, 95% CI 1.16-1.89, P = 0.002).

Conclusions

Raised CMR-modelled PCWP is an independent risk factor for incident HF and MACE. CMR-modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management.
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Rigorous exploration in 'Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: Prognostic insights.'. Groundbreaking research by Thomson & team published:
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The Society for Cardiovascular Magnetic Resonance Registry at 150,000.

Open Access Issue 2 Vol 26 Published on 2024-12-01 PMID 38971501 PMCID PMC11314894
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Keywords: Infarction, Registry, Cardiovascular Magnetic Resonance, Late Gadolinium Enhancement, Real-world Evidence
DOI: https://doi.org/10.1016/j.jocmr.2024.101055
Authors: Matthew S Tong In X Jeremy A Slivnick In X Behzad Sharif In X Han W Kim In X Alistair A Young In X Lilia M Sierra-Galan In X Kanae Mukai In X Afshin Farzaneh-Far In X Sadeer Al-Kindi In X Angel T Chan In X George Dibu In X Michael D Elliott In X Vanessa M Ferreira In X John Grizzard In X Sebastian Kelle In X Simon Lee In X Maan Malahfji In X Steffen E Petersen In X Venkateshwar Polsani In X Olga H Toro-Salazar In X Kamran A Shaikh In X Chetan Shenoy In X Monvadi B Srichai In X Jadranka Stojanovska In X Qian Tao In X Janet Wei In X Jonathan W Weinsaft In X W Benjamin Wince In X Priya D Chudgar In X Matthew Judd In X Robert M Judd In X Dipan J Shah In X Orlando P Simonetti In X
Abstract:

Background

Cardiovascular magnetic resonance (CMR) is increasingly utilized to evaluate expanding cardiovascular conditions. The Society for Cardiovascular Magnetic Resonance (SCMR) Registry is a central repository for real-world clinical data to support cardiovascular research, including those relating to outcomes, quality improvement, and machine learning. The SCMR Registry is built on a regulatory-compliant, cloud-based infrastructure that houses searchable content and Digital Imaging and Communications in Medicine images. The goal of this study is to summarize the status of the SCMR Registry at 150,000 exams.

Methods

The processes for data security, data submission, and research access are outlined. We interrogated the Registry and presented a summary of its contents.

Results

Data were compiled from 154,458 CMR scans across 20 United States sites, containing 299,622,066 total images (∼100 terabytes of storage). Across reported values, the human subjects had an average age of 58 years (range 1 month to >90 years old), were 44% (63,070/145,275) female, 72% (69,766/98,008) Caucasian, and had a mortality rate of 8% (9,962/132,979). The most common indication was cardiomyopathy (35,369/131,581, 27%), and most frequently used current procedural terminology code was 75561 (57,195/162,901, 35%). Macrocyclic gadolinium-based contrast agents represented 89% (83,089/93,884) of contrast utilization after 2015. Short-axis cines were performed in 99% (76,859/77,871) of tagged scans, short-axis late gadolinium enhancement (LGE) in 66% (51,591/77,871), and stress perfusion sequences in 30% (23,241/77,871). Mortality data demonstrated increased mortality in patients with left ventricular ejection fraction <35%, the presence of wall motion abnormalities, stress perfusion defects, and infarct LGE, compared to those without these markers. There were 456,678 patient-years of all-cause mortality follow-up, with a median follow-up time of 3.6 years.

Conclusion

The vision of the SCMR Registry is to promote evidence-based utilization of CMR through a collaborative effort by providing a web mechanism for centers to securely upload de-identified data and images for research, education, and quality control. The Registry quantifies changing practice over time and supports large-scale real-world multicenter observational studies of prognostic utility.
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Characterisation of patients who develop atrial fibrillation-induced cardiomyopathy.

Open Access Issue 2 Vol 11 Published on 2024-11-01 PMID 39608861 PMCID PMC11603700
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Keywords: Atrial fibrillation, Catheter ablation, Cardiomyopathies
DOI: https://doi.org/10.1136/openhrt-2024-002955
Authors: Nikhil Ahluwalia In X Shohreh Honarbakhsh In X Hakam Abbass In X Abhishek Joshi In X Anthony W C Chow In X Mehul Dhinoja In X Steffen Erhard Petersen In X Ross J Hunter In X Guy Lloyd In X Richard J Schilling In X
Abstract:

Introduction

Atrial fibrillation (AF)-induced cardiomyopathy (AIC) is retrospectively defined after normalisation of left ventricular ejection fraction (LVEF) in sinus rhythm. It is unclear why some patients develop AIC.

Hypothesis

Patients with AIC have a subtle cardiomyopathic process that precedes their AF-mediated LVEF reduction. Detailed assessment of cardiac function after successful catheter ablation will reveal this.

Objective

To evaluate the utility of measures to identify cardiomyopathic features that persist after LVEF normalisation in AIC.

Methods

Patients with rate-controlled persistent AF and LVEF<50% undergoing catheter ablation (CA) were prospectively evaluated using echocardiography, cardio-pulmonary exercise testing and serum N-terminal pro b-type natriuretic peptide (NT-proBNP) at baseline and 6 months after CA. Participants with AIC, (LVEF recovery (≥50%) and no other cause for cardiac dysfunction) were evaluated using left ventricular (LV) longitudinal strain and left atrial (LA) reservoir strain (LARS). Changes in peak oxygen consumption and the minute ventilation/carbon dioxide production slope were measured as markers of functional capacity and ventilatory inefficiency. A control group of patients with persistent AF with preserved LVEF were also enrolled.

Results

34/41 (82.9%) participants recovered LVEF in sinus rhythm; defined as AIC. NT-proBNP levels were elevated in 18 (52.9%), and 16 reported ongoing heart failure (HF) symptoms. 10 (29.4%) had no improvement in functional capacity, and seven (20.6%) showed persistent ventilatory inefficiency. 20 (58.8%) had impaired global LV longitudinal strain with a relative apical sparing pattern. Nine (26.5%) had impaired LARS. There was an overlap of these abnormalities. 32 (94.1%) demonstrated at least one, 17 (50.0%) having no cardiovascular risk factors. Patients with preserved LVEF during persistent AF had similar demographics but a lower burden of short R-R intervals (<660 ms) on Holter monitoring.

Discussion

Abnormal structural, metabolic and HF biomarkers are seen in patients with AIC in sinus rhythm. These features may represent a precedent subtle cardiomyopathic process predisposing them to left ventricular systolic dysfunction in AF.

Trial registration number

NCT04987723.
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Routine measurement of cardiometabolic disease risk factors in primary care in England before, during, and after the COVID-19 pandemic: A population-based cohort study.

Open Access Issue 11 Vol 21 Published on 2024-11-01 PMID 39591388 PMCID PMC11593757
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Keywords:
DOI: https://doi.org/10.1371/journal.pmed.1004485
Authors: Frederick K Ho In X Caroline Dale In X Mehrdad A Mizani In X Thomas Bolton In X Ewan R Pearson In X Jonathan Valabhji In X Christian Delles In X Paul Welsh In X Shinya Nakada In X Daniel Mackay In X Jill P Pell In X Chris Tomlinson In X Steffen E Petersen In X Benjamin Bray In X Mark Ashworth In X Kazem Rahimi In X Mamas Mamas In X Julian Halcox In X Cathie Sudlow In X Reecha Sofat In X Naveed Sattar In X In X
Abstract:

Background

This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels.

Methods and findings

A cohort of individuals aged ≥18 years in England with records in the primary care-COVID-19 General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR) were identified. Their records of 12 risk factor measurements were extracted between November 2018 and March 2024. Number of measurements per 1,000 individuals were calculated by age group, sex, ethnicity, and area deprivation quintile. The observed number of measurements were compared to a composite expectation band, derived as the union of the 95% confidence intervals of 2 estimates: (1) a projected trend based on data prior to the COVID-19 pandemic; and (2) an assumed stable trend from before pandemic. Point estimates were calculated as the mid-point of the expectation band. A cohort of 49,303,410 individuals aged ≥18 years were included. There was sharp drop in all measurements in March 2020 to February 2022, but overall recovered to the expected levels during March 2022 to February 2023 except for blood pressure, which had prolonged recovery. In March 2023 to March 2024, blood pressure measurements were below expectation by 16% (-19 per 1,000) overall, in people aged 18 to 39 (-23%; -18 per 1,000), 60 to 79 (-17%; -27 per 1,000), and ≥80 (-31%; -57 per 1,000). There was suggestion that recovery in blood pressure measurements was socioeconomically patterned. The second most deprived quintile had the highest deviation (-20%; -23 per 1,000) from expectation compared to least deprived quintile (-13%; -15 per 1,000).

Conclusions

There was a substantial reduction in routine measurements of cardiometabolic risk factors following the COVID-19 pandemic, with variable recovery. The implications for missed diagnoses, worse prognosis, and health inequality are a concern.
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Genetic basis of right and left ventricular heart shape.

Open Access Issue 1 Vol 15 Published on 2024-11-01 PMID 39543113 PMCID PMC11564811
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Keywords:
DOI: https://doi.org/10.1038/s41467-024-53594-7
Authors: Richard Burns In X William J Young In X Nay Aung In X Luis R Lopes In X Perry M Elliott In X Petros Syrris In X Roberto Barriales-Villa In X Catrin Sohrabi In X Steffen E Petersen In X Julia Ramírez In X Alistair Young In X Patricia B Munroe In X
Abstract: Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis is less understood. We utilised cardiovascular magnetic resonance images from 45,683 UK Biobank participants to construct a heart shape atlas from bi-ventricular end-diastolic surface mesh models through principal component (PC) analysis. Genome-wide association studies were performed on the first 11 PCs that captured 83.6% of shape variance. We identified 43 significant loci, 14 were previously unreported for cardiac traits. Genetically predicted PCs were associated with cardiometabolic diseases. In particular two PCs (2 and 3) linked with more spherical ventricles being associated with increased risk of atrial fibrillation. Our study explores the genetic basis of multidimensional bi-ventricular heart shape using PCA, reporting new loci and biology, as well as polygenic risk scores for exploring genetic relationships of heart shape with cardiometabolic diseases.
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Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Issue 11 Vol 9 Published on 2024-11-01 PMID 39486903 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/s2468-2667(24)00215-9
Authors: Robert A Fletcher In X Patrick Rockenschaub In X Brendon L Neuen In X Isabel Johanna Walter In X Nathalie Conrad In X Mehrdad A Mizani In X Thomas Bolton In X Claire A Lawson In X Christopher Tomlinson In X Stelios Boulitsakis Logothetis In X Carmen Petitjean In X Luigi Filippo Brizzi In X Stephen Kaptoge In X Elena Raffetti In X Patrick A Calvert In X Emanuele Di Angelantonio In X Amitava Banerjee In X Mamas A Mamas In X Iain Squire In X Spiros Denaxas In X Theresa A McDonagh In X Cathie Sudlow In X Steffen E Petersen In X Glenn M Chertow In X Kamlesh Khunti In X Johan Sundström In X Clare Arnott In X John G F Cleland In X John Danesh In X John J V McMurray In X Muthiah Vaduganathan In X Angela M Wood In X In X
Abstract:

Background

Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised.

Methods

In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions.

Findings

Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease.

Interpretation

Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated.

Funding

Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.
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Prevalence, Cardiac Phenotype, and Outcomes of Transthyretin Variants in the UK Biobank Population.

Issue 11 Vol 9 Published on 2024-11-01 PMID 39196575 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1001/jamacardio.2024.2190
Authors: Nay Aung In X Hannah L Nicholls In X C Anwar A Chahal In X Mohammed Y Khanji In X Elisa Rauseo In X Sucharitha Chadalavada In X Steffen E Petersen In X Patricia B Munroe In X Perry M Elliott In X Luis R Lopes In X
Abstract:

Importance

The population prevalence of cardiac transthyretin amyloidosis (ATTR) caused by pathogenic variation in the TTR gene (vATTR) is unknown.

Objective

To estimate the population prevalence of disease-causing TTR variants and evaluate associated phenotypes and outcomes.

Design, setting, and participants

This population-based cohort study analyzed UK Biobank (UKB) participants with whole-exome sequencing, electrocardiogram, and cardiovascular magnetic resonance data. Participants were enrolled from 2006 to 2010, with a median follow-up of 12 (IQR, 11-13) years (cutoff date for the analysis, March 12, 2024). Sixty-two candidate TTR variants were extracted based on rarity (minor allele frequency ≤0.0001) and/or previously described associations with amyloidosis if more frequent.

Exposure

Carrier status for TTR variants.

Main outcomes and measures

Associations of TTR carrier status with vATTR prevalence and cardiovascular imaging and electrocardiogram traits were explored using descriptive statistics. Associations between TTR carrier status and atrial fibrillation, conduction disease, heart failure, and all-cause mortality were evaluated using adjusted Cox proportional hazards models. Genotypic and diagnostic concordance was examined using International Statistical Classification of Diseases, Tenth Revision codes from the hospital record.

Results

The overall cohort included 469 789 UKB participants (mean [SD] age, 56.5 [8.1] years; 54.2% female and 45.8% male). A likely pathogenic/pathogenic (LP/P) TTR variant was detected in 473 (0.1%) participants, with Val142Ile being the most prevalent (367 [77.6%]); 91 individuals (0.02%) were carriers of a variant of unknown significance . The overall prevalence of LP/P variants was 0.02% (105 of 444 243) in participants with European ancestry and 4.3% (321 of 7533) in participants with African ancestry. The LP/P variants were associated with higher left ventricular mass indexed to body surface area (β = 4.66; 95% CI, 1.87-7.44), and Val142Ile was associated with a longer PR interval (β = 18.34; 95% CI, 5.41-31.27). The LP/P carrier status was associated with a higher risk of heart failure (hazard ratio [HR], 2.68; 95% CI, 1.75-4.12) and conduction disease (HR, 1.88; 95% CI, 1.25-2.83). Higher all-cause mortality risk was observed for non-Val142Ile LP/P variants (HR, 1.98; 95% CI, 1.06-3.67). Thirteen participants (2.8%) with LP/P variants had diagnostic codes compatible with cardiac or neurologic amyloidosis. Variants of unknown significance were not associated with outcomes.

Conclusions and relevance

This study found that approximately 1 in 1000 UKB participants were LP/P TTR variant carriers, exceeding previously reported prevalence. The findings emphasize the need for clinical vigilance in identifying individuals at risk of developing vATTR and associated poor outcomes.
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Characterizing the Contribution of Dependent Features in XAI Methods.

Issue 11 Vol 28 Published on 2024-11-01 PMID 38696291 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1109/jbhi.2024.3395289
Authors: Ahmed M Salih In X Ilaria Boscolo Galazzo In X Zahra Raisi-Estabragh In X Steffen E Petersen In X Gloria Menegaz In X Petia Radeva In X
Abstract: Explainable Artificial Intelligence (XAI) provides tools to help understanding how AI models work and reach a particular decision or outcome. It helps to increase the interpretability of models and makes them more trustworthy and transparent. In this context, many XAI methods have been proposed to make black-box and complex models more digestible from a human perspective. However, one of the main issues that XAI methods have to face especially when dealing with a high number of features is the presence of multicollinearity, which casts shadows on the robustness of the XAI outcomes, such as the ranking of informative features. Most of the current XAI methods either do not consider the collinearity or assume the features are independent which, in general, is not necessarily true. Here, we propose a simple, yet useful, proxy that modifies the outcome of any XAI feature ranking method allowing to account for the dependency among the features, and to reveal their impact on the outcome. The proposed method was applied to SHAP, as an example of XAI method which assume that the features are independent. For this purpose, several models were exploited for a well-known classification task (males versus females) using nine cardiac phenotypes extracted from cardiac magnetic resonance imaging as features. Principal component analysis and biological plausibility were employed to validate the proposed method. Our results showed that the proposed proxy could lead to a more robust list of informative features compared to the original SHAP in presence of collinearity.
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Health data science course for clinicians: Time to bridge the skills gap?

Issue N/A Vol N/A Published on 2024-10-01 PMID 39392939 PMCID N/A
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Keywords: Medical education, Big Data, R Programming, Data Science, Health Data Science, Data Science Course
DOI: https://doi.org/10.1177/02676591241291946
Authors: Hafiz Naderi In X Yu-Hsuen Yang In X Patricia B Munroe In X Steffen E Petersen In X Mark Westwood In X Nay Aung In X
Abstract:

Background

Data science skills are highly relevant for clinicians working in an era of big data in healthcare. However, these skills are not routinely taught, representing a growing unmet educational need. This education report presents a structured short course that was run to teach clinicians data science and the lessons learnt.

Methods

A 1-day introductory course was conducted within a tertiary hospital in London. It consisted of lectures followed by facilitated pair programming exercises in R, an object-oriented programming language. Feedback was collated and participant responses were graded using a Likert scale.

Results

The course was attended by 20 participants. The majority of participants (69%) were in higher speciality cardiology training. While more than half of the participants (56%) received prior training in statistics either through formal taught programmes (e.g., a Master's degree) or online courses, the participants reported several barriers to expanding their skills in data science due to limited programming skills, lack of dedicated time, training opportunities and awareness. After the short course, there was a significant increase in participants' self-rated confidence in using R for data analysis (mean response; before the course: 1.69 ± 1.0, after the course: 3.2 ± 0.9, p = .0005) and awareness of the capabilities of R (mean response; before the course: 2.1 ± 0.9, after the course: 3.6 ± 0.7, p = .0001, on a 5-point Likert scale).

Conclusion

This proof-of-concept study demonstrates that a structured short course can effectively introduce data science skills to clinicians and supports future educational initiatives to integrate data science teaching into medical education.
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The Association Between Periodontal Disease and Cardiovascular Disease: Insights From Imaging, Observational, and Genetic Data.

Open Access Issue 10 Vol 3 Published on 2024-10-01 PMID 39290820 PMCID PMC11406040
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Keywords: Cardiovascular risk factors, periodontal disease, coronary artery disease, Cardiovascular Magnetic Resonance
DOI: https://doi.org/10.1016/j.jacadv.2024.101241
Authors: Mihir M Sanghvi In X Julia Ramírez In X Sucharitha Chadalavada In X Nay Aung In X Patricia B Munroe In X Nikolaos Donos In X Steffen E Petersen In X
Abstract:

Background

Periodontal disease is the sixth most common disease worldwide and may be a contributory risk factor for cardiovascular disease (CVD).

Objectives

This study utilizes noninvasive cardiac imaging and longitudinal and genetic data to characterize the association between periodontal disease and both cardiovascular magnetic resonance (CMR) imaging biomarkers of remodeling and incident coronary artery disease (CAD).

Methods

From the UK Biobank, 481,915 individuals were included, 91,022 (18.9%) of whom had self-reported periodontal disease. For imaging analysis, 59,019 had paired CMR data. Multivariable linear regression models were constructed to examine the association of periodontal disease on CMR outcomes. The endpoints for the CMR analyses were left ventricle (LV) end-diastolic volume, LV ejection fraction, LV mass, LV mass:volume ratio, LV global longitudinal strain, and native T1 values. The relationship between periodontal disease and CVD was assessed using Cox proportional hazards regression models, with incident CAD as the endpoint. To examine the relationship of genetically determined periodontal disease on CAD, a genome-wide polygenic risk score was constructed.

Results

Periodontal disease was associated with a significantly higher LV mass:volume ratio (effect size: 0.00233; 95% CI: 0.0006-0.004) and significantly lower T1 values (effect size: -0.86 ms; 95% CI: -1.63 to -0.09). Periodontal disease was independently associated with an increased hazard of incident CAD (HR: 1.09; 95% CI: 1.07-1.13) at a median follow-up time of 13.8 years. Each SD increase in the periodontal disease polygenic risk score was associated with increased odds of CAD (OR: 1.03; 95% CI: 1.02-1.05).

Conclusions

Using an integrated approach across imaging, observational, and genomic data, periodontal disease is associated with biomarkers of subclinical remodeling as well as incident CAD. These findings highlight the potential importance of periodontal disease in the broader context of CVD prevention.
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Multimodality imaging for the evaluation and management of patients with long-term (durable) left ventricular assist devices.

Issue 10 Vol 25 Published on 2024-09-01 PMID 38965039 PMCID N/A
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Keywords: Echocardiography, Heart Failure, computed tomography, Cardiac Magnetic Resonance, Cardiac Imaging, Left Ventricular Assist Device
DOI: https://doi.org/10.1093/ehjci/jeae165
Authors: Matteo Cameli In X Hatem Soliman Aboumarie In X Maria Concetta Pastore In X Kadir Caliskan In X Maja Cikes In X Madalina Garbi In X Hoong Sern Lim In X Denisa Muraru In X Giulia Elena Mandoli In X Valeria Pergola In X Sven Plein In X Gianluca Pontone In X Osama I Soliman In X Pal Maurovich-Horvat In X Erwan Donal In X Bernard Cosyns In X Steffen E Petersen In X In X
Abstract: Left ventricular assist devices (LVADs) are gaining increasing importance as therapeutic strategy in advanced heart failure (HF), not only as bridge to recovery or to transplant but also as destination therapy. Even though long-term LVADs are considered a precious resource to expand the treatment options and improve clinical outcome of these patients, these are limited by peri-operative and post-operative complications, such as device-related infections, haemocompatibility-related events, device mis-positioning, and right ventricular failure. For this reason, a precise pre-operative, peri-operative, and post-operative evaluation of these patients is crucial for the selection of LVAD candidates and the management LVAD recipients. The use of different imaging modalities offers important information to complete the study of patients with LVADs in each phase of their assessment, with peculiar advantages/disadvantages, ideal application, and reference parameters for each modality. This clinical consensus statement sought to guide the use of multimodality imaging for the evaluation of patients with advanced HF undergoing LVAD implantation.
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Principles of cortical areas and their implications for neuroimaging.

Issue 17 Vol 112 Published on 2024-09-01 PMID 38834069 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.neuron.2024.05.008
Authors: Steven E Petersen In X Benjamin A Seitzman In X Steven M Nelson In X Gagan S Wig In X Evan M Gordon In X
Abstract: Cortical organization should constrain the study of how the brain performs behavior and cognition. A fundamental concept in cortical organization is that of arealization: that the cortex is parceled into discrete areas. In part one of this report, we review how non-human animal studies have illuminated principles of cortical arealization by revealing: (1) what defines a cortical area, (2) how cortical areas are formed, (3) how cortical areas interact with one another, and (4) what "computations" or "functions" areas perform. In part two, we discuss how these principles apply to neuroimaging research. In doing so, we highlight several examples where the commonly accepted interpretation of neuroimaging observations requires assumptions that violate the principles of arealization, including nonstationary areas that move on short time scales, large-scale gradients as organizing features, and cortical areas with singular functionality that perfectly map psychological constructs. Our belief is that principles of neurobiology should strongly guide the nature of computational explanations.
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Global longitudinal active strain energy density (GLASED): a powerful prognostic marker in a community-based cohort.

Open Access Issue 10 Vol 25 Published on 2024-09-01 PMID 38768297 PMCID PMC11441035
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Keywords: Energy, contractility, Heart Failure, Systolic Function, Contractile Function, Stroke Work, Contractance
DOI: https://doi.org/10.1093/ehjci/jeae133
Authors: Nay Aung In X David H MacIver In X Henggui Zhang In X Sucharitha Chadalavada In X Steffen E Petersen In X
Abstract:

Aims

Identifying the imaging method that best predicts all-cause mortality, cardiovascular adverse events, and heart failure risk is crucial for tailoring optimal management. Potential prognostic markers include left ventricular (LV) myocardial mass, ejection fraction, myocardial strain, stroke work, contraction fraction, pressure-strain product, and a new measurement called global longitudinal active strain density (GLASED). This study sought to compare the utility of 23 potential LV prognostic markers of structure and contractile function in a community-based cohort.

Methods and results

The impact of cardiovascular magnetic resonance image-derived markers extracted by machine learning algorithms was compared with the future risk of adverse events in a group of 44 957 UK Biobank participants. Most markers, including the LV ejection fraction, have limited prognostic value. GLASED was significantly associated with all-cause mortality and major adverse cardiovascular events, with the largest hazard ratio, highest ranking, and differentiated risk in all three tertiles (P ≤ 0.0003).

Conclusion

GLASED predicted all-cause mortality and major cardiovascular adverse events better than conventional markers of risk and is recommended for assessing patient prognosis.
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Evaluation of deep learning estimation of whole heart anatomy from automated cardiovascular magnetic resonance short- and long-axis analyses in UK Biobank.

Open Access Issue 10 Vol 25 Published on 2024-09-01 PMID 38723059 PMCID PMC11441036
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Keywords: Regression, risk factors, Deep Learning, Disease Factors, Volume Estimates, Dense Segmentations
DOI: https://doi.org/10.1093/ehjci/jeae123
Authors: Marica Muffoletto In X Hao Xu In X Richard Burns In X Avan Suinesiaputra In X Anastasia Nasopoulou In X Karl P Kunze In X Radhouene Neji In X Steffen E Petersen In X Steven A Niederer In X Daniel Rueckert In X Alistair A Young In X
Abstract:

Aims

Standard methods of heart chamber volume estimation in cardiovascular magnetic resonance (CMR) typically utilize simple geometric formulae based on a limited number of slices. We aimed to evaluate whether an automated deep learning neural network prediction of 3D anatomy of all four chambers would show stronger associations with cardiovascular risk factors and disease than standard volume estimation methods in the UK Biobank.

Methods and results

A deep learning network was adapted to predict 3D segmentations of left and right ventricles (LV, RV) and atria (LA, RA) at ∼1 mm isotropic resolution from CMR short- and long-axis 2D segmentations obtained from a fully automated machine learning pipeline in 4723 individuals with cardiovascular disease (CVD) and 5733 without in the UK Biobank. Relationships between volumes at end-diastole (ED) and end-systole (ES) and risk/disease factors were quantified using univariate, multivariate, and logistic regression analyses. Strength of association between deep learning volumes and standard volumes was compared using the area under the receiving operator characteristic curve (AUC). Univariate and multivariate associations between deep learning volumes and most risk and disease factors were stronger than for standard volumes (higher R2 and more significant P-values), particularly for sex, age, and body mass index. AUCs for all logistic regressions were higher for deep learning volumes than standard volumes (P < 0.001 for all four chambers at ED and ES).

Conclusion

Neural network reconstructions of whole heart volumes had significantly stronger associations with CVD and risk factors than standard volume estimation methods in an automatic processing pipeline.
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Feasibility of multiorgan risk prediction with routinely collected diagnostics: a prospective cohort study in the UK Biobank.

Open Access Issue 5 Vol 29 Published on 2024-09-01 PMID 38719437 PMCID PMC11503151
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Keywords: General Practice, Primary Care, Primary Healthcare
DOI: https://doi.org/10.1136/bmjebm-2023-112518
Authors: Celeste McCracken In X Zahra Raisi-Estabragh In X Liliana Szabo In X Michele Veldsman In X Betty Raman In X Anya Topiwala In X Adriana Roca-Fernández In X Masud Husain In X Steffen E Petersen In X Stefan Neubauer In X Thomas E Nichols In X
Abstract:

Objectives

Despite rising rates of multimorbidity, existing risk assessment tools are mostly limited to a single outcome of interest. This study tests the feasibility of producing multiple disease risk estimates with at least 70% discrimination (area under the receiver operating curve, AUROC) within the time and information constraints of the existing primary care health check framework.

Design

Observational prospective cohort study SETTING: UK Biobank.

Participants

228 240 adults from the UK population.

Interventions

None.

Main outcome measures

Myocardial infarction, atrial fibrillation, heart failure, stroke, all-cause dementia, chronic kidney disease, fatty liver disease, alcoholic liver disease, liver cirrhosis and liver failure.

Results

Using a set of predictors easily gathered at the standard primary care health check (such as the National Health Service Health Check), we demonstrate that it is feasible to simultaneously produce risk estimates for multiple disease outcomes with AUROC of 70% or greater. These predictors can be entered once into a single form and produce risk scores for stroke (AUROC 0.727, 95% CI 0.713 to 0.740), all-cause dementia (0.823, 95% CI 0.810 to 0.836), myocardial infarction (0.785, 95% CI 0.775 to 0.795), atrial fibrillation (0.777, 95% CI 0.768 to 0.785), heart failure (0.828, 95% CI 0.818 to 0.838), chronic kidney disease (0.774, 95% CI 0.765 to 0.783), fatty liver disease (0.766, 95% CI 0.753 to 0.779), alcoholic liver disease (0.864, 95% CI 0.835 to 0.894), liver cirrhosis (0.763, 95% CI 0.734 to 0.793) and liver failure (0.746, 95% CI 0.695 to 0.796).

Conclusions

Easily collected diagnostics can be used to assess 10-year risk across multiple disease outcomes, without the need for specialist computing or invasive biomarkers. Such an approach could increase the utility of existing data and place multiorgan risk information at the fingertips of primary care providers, thus creating opportunities for longer-term multimorbidity prevention. Additional work is needed to validate whether these findings would hold in a larger, more representative cohort outside the UK Biobank.
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Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank.

Open Access Issue 4 Vol 6 Published on 2024-08-01 PMID 39239345 PMCID PMC11372025
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Keywords: Cohort studies, Preventive Medicine, Cardiovascular Risk Score, Cancer Survivors, Cardio-oncology
DOI: https://doi.org/10.1016/j.jaccao.2024.05.015
Authors: Celeste McCracken In X Dorina-Gabriela Condurache In X Liliana Szabo In X Hussein Elghazaly In X Fiona M Walter In X Adam J Mead In X Ronjon Chakraverty In X Nicholas C Harvey In X Charlotte H Manisty In X Steffen E Petersen In X Stefan Neubauer In X Zahra Raisi-Estabragh In X
Abstract:

Background

Cardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts.

Objectives

This study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank.

Methods

The predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported.

Results

The analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls.

Conclusions

Existing cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.
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Myocardial Strain Measured by Cardiac Magnetic Resonance Predicts Cardiovascular Morbidity and Death.

Open Access Issue 7 Vol 84 Published on 2024-08-01 PMID 39111972 PMCID PMC11320766
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Keywords: Survival analysis, Cardiac Magnetic Resonance, Longitudinal Strain, Circumferential Strain, Radial Strain
DOI: https://doi.org/10.1016/j.jacc.2024.05.050
Authors: Sucharitha Chadalavada In X Kenneth Fung In X Elisa Rauseo In X Aaron M Lee In X Mohammed Y Khanji In X Alborz Amir-Khalili In X Jose Paiva In X Hafiz Naderi In X Shantanu Banik In X Mihaela Chirvasa In X Magnus T Jensen In X Nay Aung In X Steffen E Petersen In X
Abstract:

Background

Myocardial strain using cardiac magnetic resonance (CMR) is a sensitive marker for predicting adverse outcomes in many cardiac disease states, but the prognostic value in the general population has not been studied conclusively.

Objectives

The goal of this study was to assess the independent prognostic value of CMR feature tracking (FT)-derived LV global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) metrics in predicting adverse outcomes (heart failure, myocardial infarction, stroke, and death).

Methods

Participants from the UK Biobank population imaging study were included. Univariable and multivariable Cox models were used for each outcome and each strain marker (GLS, GCS, GRS) separately. The multivariable models were tested with adjustment for prognostically important clinical features and conventional global LV imaging markers relevant for each outcome.

Results

Overall, 45,700 participants were included in the study (average age 65 ± 8 years), with a median follow-up period of 3 years. All univariable and multivariable models demonstrated that lower absolute GLS, GCS, and GRS were associated with increased incidence of heart failure, myocardial infarction, stroke, and death. All strain markers were independent predictors (incrementally above some respective conventional LV imaging markers) for the morbidity outcomes, but only GLS predicted death independently: (HR: 1.18; 95% CI: 1.07-1.30).

Conclusions

In the general population, LV strain metrics derived using CMR-FT in radial, circumferential, and longitudinal directions are strongly and independently predictive of heart failure, myocardial infarction, and stroke, but only GLS is independently predictive of death in an adult population cohort.
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Management of cardiac sarcoidosis.

Issue 30 Vol 45 Published on 2024-08-01 PMID 38923509 PMCID N/A
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Keywords: Screening, Management, Diagnosis, epidemiology, immunosuppression, Multidisciplinary, Cardiac Sarcoidosis
DOI: https://doi.org/10.1093/eurheartj/ehae356
Authors: Rakesh Sharma In X Vasileios Kouranos In X Leslie T Cooper In X Marco Metra In X Arsen Ristic In X Bettina Heidecker In X John Baksi In X Eleanor Wicks In X Jose L Merino In X Karin Klingel In X Massimo Imazio In X Christian de Chillou In X Carsten Tschöpe In X Petr Kuchynka In X Steffen E Petersen In X Theresa McDonagh In X Thomas Lüscher In X Gerasimos Filippatos In X
Abstract: Cardiac sarcoidosis (CS) is a form of inflammatory cardiomyopathy associated with significant clinical complications such as high-degree atrioventricular block, ventricular tachycardia, and heart failure as well as sudden cardiac death. It is therefore important to provide an expert consensus statement summarizing the role of different available diagnostic tools and emphasizing the importance of a multidisciplinary approach. By integrating clinical information and the results of diagnostic tests, an accurate, validated, and timely diagnosis can be made, while alternative diagnoses can be reasonably excluded. This clinical expert consensus statement reviews the evidence on the management of different CS manifestations and provides advice to practicing clinicians in the field on the role of immunosuppression and the treatment of cardiac complications based on limited published data and the experience of international CS experts. The monitoring and risk stratification of patients with CS is also covered, while controversies and future research needs are explored.
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Social media for cardiac imagers: a review.

Open Access Issue 9 Vol 25 Published on 2024-08-01 PMID 38650541 PMCID PMC11346354
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Keywords: Cardiology, Publications, Social Media, Cardiac Imaging Techniques, Networking
DOI: https://doi.org/10.1093/ehjci/jeae109
Authors: Mark J Schuuring In X Shehab Anwer In X Steffen E Petersen In X Sarah Moharem-Elgamal In X Denisa Muraru In X
Abstract: Cardiac imaging plays a pivotal role in the diagnosis and management of cardiovascular diseases. In the burgeoning landscape of digital technology and social media platforms, it becomes essential for cardiac imagers to know how to effectively increase the visibility and the impact of their activity. With the availability of social sites like X (formerly Twitter), Instagram, and Facebook, cardiac imagers can now reach a wider audience and engage with peers, sharing their findings, insights, and discussions. The integration of persistent identifiers, such as digital object identifiers (DOIs), facilitates traceability and citation of cardiac imaging publications across various digital platforms, further enhancing their discoverability. To maximize visibility, practical advice is provided, including the use of visually engaging infographics and videos, as well as the strategic implementation of relevant hashtags and keywords. These techniques can significantly improve the discoverability of cardiac imaging research through search engine optimization and social media algorithms. Tracking impact and engagement is crucial in the digital age, and this review discusses various metrics and tools to gauge the reach and influence of cardiac imaging publications. This includes traditional citation-based metrics and altmetrics. Moreover, this review underscores the importance of creating and updating professional profiles on social platforms and participating in relevant scientific communities online. The adoption of digital technology, social platforms, and a strategic approach to publication sharing can empower cardiac imaging professionals to enhance the visibility and impact of their research, ultimately advancing the field and improving patient care.
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The association between adverse childhood experiences and adult cardiac function in the UK Biobank.

Open Access Issue 3 Vol 2 Published on 2024-07-01 PMID 39741927 PMCID PMC11686440
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Keywords: Child Abuse, Neglect, Cardiovascular Magnetic Resonance, Cardiac Remodelling, Childhood Maltreatment, Cardiovascular Imaging Phenotypes
DOI: https://doi.org/10.1093/ehjimp/qyae139
Authors: Juan C Quiroz In X Jackie Cooper In X Celeste McCracken In X Mohammed Y Khanji In X Liliana Laranjo In X Nay Aung In X Aaron Mark Lee In X Judit Simon In X Theodore Murphy In X Luca Biasiolli In X Stefan K Piechnik In X Pal Maurovich-Horvat In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Aims

The importance of early life factors in determining health in later adulthood is increasingly recognized. This study evaluated the association of adverse childhood experiences (ACEs) with cardiovascular magnetic resonance (CMR) phenotypes.

Methods and results

UK Biobank participants who had completed CMR and the self-reported questionnaire on traumatic childhood experiences were included. Images were analysed using automated pipelines to extract measures of left and right ventricular (LV and RV) structure and function, myocardial character, and arterial compliance. Multivariable linear regression was used to estimate the association of childhood adversity with CMR phenotypes adjusting for age, sex, deprivation, education, obesity, smoking, alcohol intake, exercise level, diabetes, hypertension, and hypercholesterolaemia. Amongst 30 814 participants analysed, 6023 (19.5%) experienced physical abuse, 2746 (8.9%) sexual abuse, 4685 (15.2%) emotional abuse, 6822 (22.1%) emotional neglect, and 4534 (14.7%) physical neglect. Except for physical abuse, women reported greater rates of childhood adversity than men. Collectively, all types of childhood adversity were associated with smaller LV and RV volumes, greater LV mass, a concentric pattern of LV remodelling, poorer LV and RV function, lower aortic compliance, and greater arterial stiffness. Sexual abuse was associated with unhealthy CMR phenotypes in age- and sex-adjusted models, but these relationships were attenuated in fully adjusted models. Physical neglect had the most prominent pattern of adverse cardiovascular remodelling.

Conclusion

ACEs were associated with unhealthy cardiovascular remodelling in adulthood, independent of traditional cardiovascular risk factors. These findings support the consideration of early life factors in cardiovascular disease risk assessment.
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Quality control of cardiac magnetic resonance imaging segmentation, feature tracking, aortic flow, and native T1 analysis using automated batch processing in the UK Biobank study.

Open Access Issue 3 Vol 2 Published on 2024-07-01 PMID 39385845 PMCID PMC11462446
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Keywords: Quality control, Machine Learning, Cardiac Magnetic Resonance Imaging, Automated Image Analysis, Shiny App
DOI: https://doi.org/10.1093/ehjimp/qyae094
Authors: Sucharitha Chadalavada In X Elisa Rauseo In X Ahmed Salih In X Hafiz Naderi In X Mohammed Khanji In X Jose D Vargas In X Aaron M Lee In X Alborz Amir-Kalili In X Lisette Lockhart In X Ben Graham In X Mihaela Chirvasa In X Kenneth Fung In X Jose Paiva In X Mihir M Sanghvi In X Gregory G Slabaugh In X Magnus T Jensen In X Nay Aung In X Steffen E Petersen In X
Abstract:

Aims

Automated algorithms are regularly used to analyse cardiac magnetic resonance (CMR) images. Validating data output reliability from this method is crucial for enabling widespread adoption. We outline a visual quality control (VQC) process for image analysis using automated batch processing. We assess the performance of automated analysis and the reliability of replacing visual checks with statistical outlier (SO) removal approach in UK Biobank CMR scans.

Methods and results

We included 1987 CMR scans from the UK Biobank COVID-19 imaging study. We used batch processing software (Circle Cardiovascular Imaging Inc.-CVI42) to automatically extract chamber volumetric data, strain, native T1, and aortic flow data. The automated analysis outputs (∼62 000 videos and 2000 images) were visually checked by six experienced clinicians using a standardized approach and a custom-built R Shiny app. Inter-observer variability was assessed. Data from scans passing VQC were compared with a SO removal QC method in a subset of healthy individuals (n = 1069). Automated segmentation was highly rated, with over 95% of scans passing VQC. Overall inter-observer agreement was very good (Gwet's AC2 0.91; 95% confidence interval 0.84, 0.94). No difference in overall data derived from VQC or SO removal in healthy individuals was observed.

Conclusion

Automated image analysis using CVI42 prototypes for UK Biobank CMR scans demonstrated high quality. Larger UK Biobank data sets analysed using these automated algorithms do not require in-depth VQC. SO removal is sufficient as a QC measure, with operator discretion for visual checks based on population or research objectives.
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Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction.

Open Access Issue 4 Vol 4 Published on 2024-07-01 PMID 39119202 PMCID PMC11306927
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Keywords: Cardiovascular disease, epidemiology, Cardiovascular Risk, Cardiovascular Magnetic Resonance, Imaging Biomarkers, Uk Biobank
DOI: https://doi.org/10.1093/ehjopen/oeae059
Authors: Celeste McCracken In X Liliana Szabo In X Zaid A Abdulelah In X Dorina-Gabriela Condurache In X Hajnalka Vago In X Thomas E Nichols In X Steffen E Petersen In X Stefan Neubauer In X Zahra Raisi-Estabragh In X
Abstract:

Aims

Disruption of the predictable symmetry of the healthy heart may be an indicator of cardiovascular risk. This study defines the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases.

Methods and results

The analysis includes 44 796 UK Biobank participants (average age 64.1 ± 7.7 years; 51.9% women). Cardiovascular magnetic resonance (CMR) metrics were derived using previously validated automated pipelines. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV and RV) end-diastolic volumes. Clinical outcomes were defined through linked health records. Incident events were those occurring for the first time after imaging, longitudinally tracked over an average follow-up time of 4.75 ± 1.52 years. The normal range for ventricular symmetry was defined in a healthy subset. Participants with values outside the 5th-95th percentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases (CVDs) were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures. Left ventricular dominance was linked to an array of pre-existing vascular risk factors and CVDs, and a two-fold increased risk of incident heart failure, non-ischaemic cardiomyopathies, and left-sided valvular disorders. Right ventricular dominance was associated with an elevated risk of all-cause mortality.

Conclusion

Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics.
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Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

Issue 7 Vol 17 Published on 2024-07-01 PMID 39012930 PMCID N/A
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Keywords: Hemodynamics, Quality of life, Cardiomyopathy, hypertrophic, Random Allocation, Cross-over Studies
DOI: https://doi.org/10.1161/circep.123.012570
Authors: James W Malcolmson In X Rebecca K Hughes In X Tim Husselbury In X Kamran Khan In X Annastazia E Learoyd In X Martin Lees In X Eleanor C Wicks In X Jamie Smith In X Alexander D Simms In X James C Moon In X Luis R Lopes In X Constantinos O'Mahony In X Neha Sekhri In X Perry M Elliott In X Steffen E Petersen In X Mehul B Dhinoja In X Saidi A Mohiddin In X
Abstract:

Background

Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms.

Methods

Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP.

Results

A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP.

Conclusions

In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO.

Registration

URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.
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Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.

Issue 7 Vol 17 Published on 2024-07-01 PMID 38613554 PMCID N/A
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Keywords: Artificial intelligence, Automated analysis, Sex differences, Ethnicity, Cardiovascular Magnetic Resonance, Healthy Reference Ranges
DOI: https://doi.org/10.1016/j.jcmg.2024.01.009
Authors: Zahra Raisi-Estabragh In X Liliana Szabo In X Celeste McCracken In X Robin Bülow In X Giovanni Donato Aquaro In X Florian Andre In X Thu-Thao Le In X Dominika Suchá In X Dorina-Gabriela Condurache In X Ahmed M Salih In X Sucharitha Chadalavada In X Nay Aung In X Aaron Mark Lee In X Nicholas C Harvey In X Tim Leiner In X Calvin W L Chin In X Matthias G Friedrich In X Andrea Barison In X Marcus Dörr In X Steffen E Petersen In X
Abstract:

Background

The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.

Objectives

This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.

Methods

CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals.

Results

The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%).

Conclusions

This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.
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Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology.

Issue 6 Vol 17 Published on 2024-06-01 PMID 38889213 PMCID N/A
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Keywords: Coronary angiography, coronary artery disease, myocardial perfusion imaging, Fractional Flow Reserve, Myocardial, Constriction, Pathologic
DOI: https://doi.org/10.1161/circimaging.124.016635
Authors: Laust Dupont Rasmussen In X Theodore Murphy In X Xenios Milidonis In X Ashkan Eftekhari In X Salma Raghad Karim In X Jelmer Westra In X Jonathan Nørtoft Dahl In X Christin Isaksen In X Lau Brix In X June Anita Ejlersen In X Mette Nyegaard In X Jane Kirk Johansen In X Hanne Maare Søndergaard In X Jesper Mortensen In X Lars Christian Gormsen In X Evald Høj Christiansen In X Amedeo Chiribiri In X Steffen E Petersen In X Morten Bøttcher In X Simon Winther In X
Abstract:

Background

Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD).

Methods

Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80).

Results

About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [P=0.03]) without compromising specificity (77% versus 74% [P=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted.

Conclusions

CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.
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Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

Issue 10444 Vol 403 Published on 2024-06-01 PMID 38823406 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/s0140-6736(24)00596-8
Authors: Kenneth Chan In X Elizabeth Wahome In X Apostolos Tsiachristas In X Alexios S Antonopoulos In X Parijat Patel In X Maria Lyasheva In X Lucy Kingham In X Henry West In X Evangelos K Oikonomou In X Lucrezia Volpe In X Michail C Mavrogiannis In X Edward Nicol In X Tarun K Mittal In X Thomas Halborg In X Rafail A Kotronias In X David Adlam In X Bhavik Modi In X Jonathan Rodrigues In X Nicholas Screaton In X Attila Kardos In X John P Greenwood In X Nikant Sabharwal In X Giovanni Luigi De Maria In X Shahzad Munir In X Elisa McAlindon In X Yogesh Sohan In X Pete Tomlins In X Muhammad Siddique In X Andrew Kelion In X Cheerag Shirodaria In X Francesca Pugliese In X Steffen E Petersen In X Ron Blankstein In X Milind Desai In X Bernard J Gersh In X Stephan Achenbach In X Peter Libby In X Stefan Neubauer In X Keith M Channon In X John Deanfield In X Charalambos Antoniades In X In X
Abstract:

Background

Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population.

Methods

This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population.

Findings

In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events.

Interpretation

The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators.

Funding

British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.
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Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.

Open Access Issue 6 Vol 8 Published on 2024-06-01 PMID 38784722 PMCID PMC11114472
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Keywords: Cardiovascular diseases, Osteoporosis, BMD, Bone Health, Cardiovascular Magnetic Resonance, Mendelian Randomization, Cardiovascular Imaging, Heel Ultrasound
DOI: https://doi.org/10.1093/jbmrpl/ziae058
Authors: Dorina-Gabriela Condurache In X Stefania D'Angelo In X Ahmed M Salih In X Liliana Szabo In X Celeste McCracken In X Adil Mahmood In X Elizabeth M Curtis In X Andre Altmann In X Steffen E Petersen In X Nicholas C Harvey In X Zahra Raisi-Estabragh In X
Abstract: This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.
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Two common and distinct forms of variation in human functional brain networks.

Issue 6 Vol 27 Published on 2024-06-01 PMID 38689142 PMCID PMC11248096
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Keywords:
DOI: https://doi.org/10.1038/s41593-024-01618-2
Authors: Ally Dworetsky In X Benjamin A Seitzman In X Babatunde Adeyemo In X Ashley N Nielsen In X Alexander S Hatoum In X Derek M Smith In X Thomas E Nichols In X Maital Neta In X Steven E Petersen In X Caterina Gratton In X
Abstract: The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most previous work treats individual differences as linked to boundary shifts between the borders of regions, here we show that cortical 'variants' also occur at a distance from their typical position, forming ectopic intrusions. Both 'border' and 'ectopic' variants are common across individuals, but differ in their location, network associations, properties of subgroups of individuals, activations during tasks, and prediction of behavioral phenotypes. Border variants also track significantly more with shared genetics than ectopic variants, suggesting a closer link between ectopic variants and environmental influences. This work argues that these two dissociable forms of variation-border shifts and ectopic intrusions-must be separately accounted for in the analysis of individual differences in cortical systems across people.
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Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.

Issue 6 Vol 34 Published on 2024-06-01 PMID 37987834 PMCID N/A
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Keywords: Pericardium, Adipose tissue, Magnetic Resonance Imaging, Machine Learning, Radiomics
DOI: https://doi.org/10.1007/s00330-023-10311-0
Authors: Liliana Szabo In X Ahmed Salih In X Esmeralda Ruiz Pujadas In X Andrew Bard In X Celeste McCracken In X Maddalena Ardissino In X Charalambos Antoniades In X Hajnalka Vago In X Pal Maurovich-Horvat In X Bela Merkely In X Stefan Neubauer In X Karim Lekadir In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.
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EACVI survey on radiation exposure in interventional echocardiography.

Open Access Issue 6 Vol 25 Published on 2024-05-01 PMID 38635738 PMCID PMC11139519
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Keywords: Survey, Radiation Exposure, Interventional Echocardiography, Eacvi, Personal Protection Device, Architectural Shielding
DOI: https://doi.org/10.1093/ehjci/jeae086
Authors: E Galli In X H Soliman-Aboumarie In X L Gargani In X P Szymański In X A Gimelli In X S E Petersen In X L E Sade In X I Stankovic In X E Donal In X B Cosyns In X E Agricola In X M R Dweck In X N Ajmone Marsan In X V Delgado In X D Muraru In X
Abstract:

Aims

The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey on radiation exposure in interventional echocardiography. The survey aimed to collect data on local practices for radioprotection in interventional echocardiography and to assess the awareness of echocardiography operators about radiation-related risks.

Methods and results

A total of 258 interventional echocardiographers from 52 different countries (48% European) responded to the survey. One hundred twenty-two (47%) participants were women. Two-thirds (76%) of interventional echocardiographers worked in tertiary care/university hospitals. Interventional echocardiography was the main clinical activity for 34% of the survey participants. The median time spent in the cath-lab for the echocardiographic monitoring of structural heart procedures was 10 (5-20) hours/month. Despite this, only 28% of interventional echocardiographers received periodic training and certification in radioprotection and 72% of them did not know their annual radiation dose. The main adopted personal protection devices were lead aprons and thyroid collars (95% and 92% of use, respectively). Dedicated architectural protective shielding was not available for 33% of interventional echocardiographers. Nearly two-thirds of responders thought that the radiation exposure of interventional echocardiographers was higher than that of interventional cardiologists and 72% claimed for an improvement in the radioprotection measures.

Conclusion

Radioprotection measures for interventional echocardiographers are widely variable across centres. Radioprotection devices are often underused by interventional echocardiographers, portending an increased radiation-related risk. International scientific societies working in the field should collaborate to endorse radioprotection training, promote reliable radiation dose assessment, and support the adoption of radioprotection shielding dedicated to interventional echocardiographers.
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Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.

Issue 5 Vol 17 Published on 2024-05-01 PMID 38597854 PMCID N/A
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Keywords: Molecular markers, Echocardiography, Cardiac Computed Tomography, Healthy Aging, Cardiac Magnetic Resonance, Multimodality Cardiovascular Imaging, Biological Heart Age
DOI: https://doi.org/10.1016/j.jcmg.2024.03.001
Authors: Zahra Raisi-Estabragh In X Liliana Szabo In X Art Schuermans In X Ahmed M Salih In X Calvin W L Chin In X Hajnalka Vágó In X Andre Altmann In X Fu Siong Ng In X Pankaj Garg In X Sofia Pavanello In X Thomas H Marwick In X Steffen E Petersen In X
Abstract: Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.
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Concurrent Left Ventricular Myocardial Diffuse Fibrosis and Left Atrial Dysfunction Strongly Predict Incident Heart Failure.

Issue 5 Vol 17 Published on 2024-05-01 PMID 38180417 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.jcmg.2023.11.006
Authors: Mark Y Z Wong In X Jose D Vargas In X Hafiz Naderi In X Mihir M Sanghvi In X Zahra Raisi-Estabragh In X Avan Suinesiaputra In X Rodrigo Bonazzola In X Rahman Attar In X Nishant Ravikumar In X Evan Hann In X Stefan Neubauer In X Stefan K Piechnik In X Alejandro F Frangi In X Steffen E Petersen In X Nay Aung In X
Abstract: No Abstract Available
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Predicted Deleterious Variants in Cardiomyopathy Genes Prognosticate Mortality and Composite Outcomes in the UK Biobank.

Issue 5 Vol 12 Published on 2024-05-01 PMID 37715771 PMCID N/A
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Keywords: Genetics, Dilated cardiomyopathy, hypertrophic cardiomyopathy, Cardiomyopathy, Sudden Cardiac Death, Arrhythmogenic Cardiomyopathy, Genotype-first Approach
DOI: https://doi.org/10.1016/j.jchf.2023.07.023
Authors: Babken Asatryan In X Ravi A Shah In X Ghaith Sharaf Dabbagh In X Andrew P Landstrom In X Dawood Darbar In X Mohammed Y Khanji In X Luis R Lopes In X Stefan van Duijvenboden In X Daniele Muser In X Aaron Mark Lee In X Christopher M Haggerty In X Pankaj Arora In X Christopher Semsarian In X Tobias Reichlin In X Virend K Somers In X Anjali T Owens In X Steffen E Petersen In X Rajat Deo In X Patricia B Munroe In X Nay Aung In X C Anwar A Chahal In X In X
Abstract:

Background

Inherited cardiomyopathies present with broad variation of phenotype. Data are limited regarding genetic screening strategies and outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the general population.

Objectives

The authors aimed to determine the risk of mortality and composite cardiomyopathy-related outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the UK Biobank.

Methods

Using whole exome sequencing data, variants in dilated, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy-associated genes with at least moderate evidence of disease causality according to ClinGen Expert Panel curations were annotated using REVEL (≥0.65) and ANNOVAR (predicted loss-of-function) considering gene-disease mechanisms. Genotype-positive and genotype-negative groups were compared using time-to-event analyses for the primary (all-cause mortality) and secondary outcomes (diagnosis of cardiomyopathy; composite outcome of diagnosis of cardiomyopathy, heart failure, arrhythmia, stroke, and death).

Results

Among 200,619 participants (age at recruitment 56.46 ± 8.1 years), 5,292 (2.64%) were found to host ≥1 predicted deleterious variants in cardiomyopathy-associated genes (CMP-G+). After adjusting for age and sex, CMP-G+ individuals had higher risk for all-cause mortality (HR: 1.13 [95% CI: 1.01-1.25]; P = 0.027), increased risk for being diagnosed with cardiomyopathy later in life (HR: 5.75 [95% CI: 4.58-7.23]; P < 0.0001), and elevated risk for composite outcome (HR: 1.29 [95% CI: 1.20-1.39]; P < 0.0001) than CMP-G- individuals. The higher risk for being diagnosed with cardiomyopathy and composite outcomes in the genotype-positive subjects remained consistent across all cardiomyopathy subgroups.

Conclusions

Adults with predicted deleterious variants in cardiomyopathy-associated genes exhibited a slightly higher risk of mortality and a significantly increased risk of developing cardiomyopathy, and cardiomyopathy-related composite outcomes, in comparison with genotype-negative controls.
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An executive-functions-based reading training enhances sensory-motor systems integration during reading fluency in children with dyslexia.

Issue 4 Vol 34 Published on 2024-04-01 PMID 38664864 PMCID N/A
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Keywords: Dyslexia, intervention, Functional Connectivity, Executive Functions, Neural Noise
DOI: https://doi.org/10.1093/cercor/bhae166
Authors: Rola Farah In X Ally Dworetsky In X Rebecca S Coalson In X Steven E Petersen In X Bradley L Schlaggar In X Keri S Rosch In X Tzipi Horowitz-Kraus In X
Abstract: The Simple View of Reading model suggests that intact language processing and word decoding lead to proficient reading comprehension, with recent studies pointing at executive functions as an important component contributing to reading proficiency. Here, we aimed to determine the underlying mechanism(s) for these changes. Participants include 120 8- to 12-year-old children (n = 55 with dyslexia, n = 65 typical readers) trained on an executive functions-based reading program, including pre/postfunctional MRI and behavioral data collection. Across groups, improved word reading was related to stronger functional connections within executive functions and sensory networks. In children with dyslexia, faster and more accurate word reading was related to stronger functional connections within and between sensory networks. These results suggest greater synchronization of brain systems after the intervention, consistent with the "neural noise" hypothesis in children with dyslexia and support the consideration of including executive functions as part of the Simple View of Reading model.
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Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.

Issue 1 Vol 311 Published on 2024-04-01 PMID 38563665 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1148/radiol.232455
Authors: Nay Aung In X Axel Bartoli In X Elisa Rauseo In X Sebastien Cortaredona In X Mihir M Sanghvi In X Joris Fournel In X Badih Ghattas In X Mohammed Y Khanji In X Steffen E Petersen In X Alexis Jacquier In X
Abstract: Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.
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Validation of 2D flow MRI for helical and vortical flows.

Open Access Issue 1 Vol 11 Published on 2024-03-01 PMID 38458769 PMCID PMC10928773
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Keywords: Aortic valve stenosis, Heart Failure, Magnetic Resonance Imaging, Aortic Diseases
DOI: https://doi.org/10.1136/openhrt-2023-002451
Authors: Zia Mehmood In X Hosamadin Assadi In X Ciaran Grafton-Clarke In X Rui Li In X Gareth Matthews In X Samer Alabed In X Rebekah Girling In X Victoria Underwood In X Bahman Kasmai In X Xiaodan Zhao In X Fabrizio Ricci In X Liang Zhong In X Nay Aung In X Steffen Erhard Petersen In X Andrew J Swift In X Vassilios S Vassiliou In X João Cavalcante In X Rob J van der Geest In X Pankaj Garg In X
Abstract:

Purpose

The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root.

Methods

This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC.

Results

For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p<0.001. A threshold of >8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p<0.001 for visual vortex flow. Manual systolic rotational flow angle change (ΔsRA) demonstrated excellent association with semiautomated ΔsRA (r=0.99, 95% CI 0.9907 to 0.999, p<0.001). In reproducibility testing, average systolic FD (FDsavg) showed a minimal bias at 1.28% with a high intraclass correlation coefficient (ICC=0.92). Similarly, sFRR had a minimal bias of 1.14% with an ICC of 0.96. ΔsRA demonstrated an acceptable bias of 5.72°-and an ICC of 0.99.

Conclusion

2D PC flow imaging can possibly quantify blood flow helicity (ΔRA) and vorticity (FRR). These imaging biomarkers of flow helicity and vorticity demonstrate high reproducibility for clinical adoption.

Trials registration number

NCT05114785.
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Cardiovascular multimodality imaging in women: a scientific statement of the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Issue 4 Vol 25 Published on 2024-03-01 PMID 38198766 PMCID N/A
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Keywords: Cardiovascular diseases, Multimodality Imaging, Cardiovascular Imaging, Women Diseases
DOI: https://doi.org/10.1093/ehjci/jeae013
Authors: Ana G Almeida In X Julia Grapsa In X Alessia Gimelli In X Chiara Bucciarelli-Ducci In X Bernhard Gerber In X Nina Ajmone-Marsan In X Anne Bernard In X Erwan Donal In X Marc R Dweck In X Kristina H Haugaa In X Krassimira Hristova In X Alicia Maceira In X Giulia Elena Mandoli In X Sharon Mulvagh In X Doralisa Morrone In X Edyta Plonska-Gosciniak In X Leyla Elif Sade In X Bharati Shivalkar In X Jeanette Schulz-Menger In X Leslee Shaw In X Marta Sitges In X Berlinde von Kemp In X Fausto J Pinto In X Thor Edvardsen In X Steffen E Petersen In X Bernard Cosyns In X In X
Abstract: Cardiovascular diseases (CVD) represent an important cause of mortality and morbidity in women. It is now recognized that there are sex differences regarding the prevalence and the clinical significance of the traditional cardiovascular (CV) risk factors as well as the pathology underlying a range of CVDs. Unfortunately, women have been under-represented in most CVD imaging studies and trials regarding diagnosis, prognosis, and therapeutics. There is therefore a clear need for further investigation of how CVD affects women along their life span. Multimodality CV imaging plays a key role in the diagnosis of CVD in women as well as in prognosis, decision-making, and monitoring of therapeutics and interventions. However, multimodality imaging in women requires specific consideration given the differences in CVD between the sexes. These differences relate to physiological changes that only women experience (e.g. pregnancy and menopause) as well as variation in the underlying pathophysiology of CVD and also differences in the prevalence of certain conditions such as connective tissue disorders, Takotsubo, and spontaneous coronary artery dissection, which are all more common in women. This scientific statement on CV multimodality in women, an initiative of the European Association of Cardiovascular Imaging of the European Society of Cardiology, reviews the role of multimodality CV imaging in the diagnosis, management, and risk stratification of CVD, as well as highlights important gaps in our knowledge that require further investigation.
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Assessing heterogeneity on cardiovascular magnetic resonance imaging: a novel approach to diagnosis and risk stratification in cardiac diseases.

Open Access Issue 4 Vol 25 Published on 2024-03-01 PMID 37982176 PMCID PMC10966332
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Keywords: Disease, Diagnosis, Cardiovascular Magnetic Resonance Imaging, Prognostication, Heterogeneity Biomarker
DOI: https://doi.org/10.1093/ehjci/jead285
Authors: Kerrick Hesse In X Mohammed Y Khanji In X Nay Aung In X Ghaith Sharaf Dabbagh In X Steffen E Petersen In X C Anwar A Chahal In X
Abstract: Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy, replacement fibrosis with akinesia in an infarct-related coronary artery territory, and a pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance (CMR) imaging mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate early diagnosis, better risk stratification, and a more comprehensive prediction of treatment response. Small cohort and case-control studies demonstrate the feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open-source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile, measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential, and radial function across the myocardium. Two of the most promising heterogeneity measures are the mean absolute deviation of regional standard deviations on native T1 and T2 and the standard deviation of time to maximum regional radial wall motion, termed the tissue synchronization index in a 16-segment left ventricle model. Real-world limitations include the non-standardization of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small, inadequately powered patient samples. We, therefore, propose a three-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies, and finally, comprehensive internal and external validations.
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Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.

Open Access Issue 2 Vol 10 Published on 2024-03-01 PMID 37218687 PMCID PMC10904726
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Keywords: Myocardial infarction, Stroke, Sex differences, risk factors
DOI: https://doi.org/10.1093/ehjqcco/qcad029
Authors: Elizabeth Remfry In X Maddalena Ardissino In X Celeste McCracken In X Liliana Szabo In X Stefan Neubauer In X Nicholas C Harvey In X Mamas A Mamas In X John Robson In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.
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Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

Open Access Issue N/A Vol 63 Published on 2024-02-01 PMID 38404218 PMCID PMC11332550
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Keywords:
DOI: https://doi.org/10.2340/1651-226x.2024.28591
Authors: Line Bjerregaard Stick In X Louise Lærke Nielsen In X Cecilia Bui Trinh In X Ihsan Bahij In X Maria Fuglsang Jensen In X Camilla Jensenius Skovhus Kronborg In X Stine Elleberg Petersen In X Linh My Hoang Thai In X May-Lin Martinsen In X Helle Precht In X Birgitte Vrou Offersen In X
Abstract:

Background and purpose

Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH.

Material and methods

Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time.

Results

All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality.

Interpretation

The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.
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Cohort Profile: The Cardiovascular Research Data Catalogue.

Issue 1 Vol 53 Published on 2024-02-01 PMID 38142238 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ije/dyad175
Authors: Jaakko Reinikainen In X Tarja Palosaari In X Alejandro J Canosa-Valls In X Carsten O Schmidt In X Rita Wissa In X Sucharitha Chadalavada In X Laia Codó In X Josep Lluís Gelpí In X Bijoy Joseph In X Aad van der Lugt In X Elsa Pacella In X Steffen E Petersen In X Esmeralda Ruiz Pujadas In X Liliana Szabo In X Tanja Zeller In X Teemu Niiranen In X Karim Lekadir In X Kari Kuulasmaa In X
Abstract: No Abstract Available
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Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry.

Issue 5 Vol 110 Published on 2024-02-01 PMID 37827557 PMCID N/A
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Keywords: Heart Failure With Preserved Ejection Fraction
DOI: https://doi.org/10.1136/heartjnl-2023-323049
Authors: In X
Abstract:

Objective

Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes.

Methods

The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction >40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort.

Conclusions

UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics.

Trial registration number

NCT05441839.
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2023 ESC Guidelines for the management of acute coronary syndromes.

Issue 1 Vol 13 Published on 2024-02-01 PMID 37740496 PMCID N/A
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Keywords: Fibrinolysis, Myocardial infarction, Unstable angina, Revascularization, Percutaneous coronary intervention, acute coronary syndrome, Recommendations, Secondary Prevention, Guidelines, Reperfusion Therapy, Antithrombotic Therapy, Patient-centred Care, St-segment Elevation Myocardial Infarction, Non-st-elevation Myocardial Infarction, Invasive Strategy, High-sensitivity Troponin, Acute Cardiac Care, Minoca
DOI: https://doi.org/10.1093/ehjacc/zuad107
Authors: Robert A Byrne In X Xavier Rossello In X J J Coughlan In X Emanuele Barbato In X Colin Berry In X Alaide Chieffo In X Marc J Claeys In X Gheorghe-Andrei Dan In X Marc R Dweck In X Mary Galbraith In X Martine Gilard In X Lynne Hinterbuchner In X Ewa A Jankowska In X Peter Jüni In X Takeshi Kimura In X Vijay Kunadian In X Margret Leosdottir In X Roberto Lorusso In X Roberto F E Pedretti In X Angelos G Rigopoulos In X Maria Rubini Gimenez In X Holger Thiele In X Pascal Vranckx In X Sven Wassmann In X Nanette Kass Wenger In X Borja Ibanez In X In X
Abstract: No Abstract Available
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Awareness of strengths and weaknesses of cardiovascular magnetic resonance imaging: results from a questionnaire survey.

Open Access Issue 1 Vol 2 Published on 2024-01-01 PMID 39403706 PMCID PMC11472751
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Keywords: Survey, Awareness, Education, Cmr, Cardiac Magnetic Resonance Imaging, Public
DOI: https://doi.org/10.1093/ehjimp/qyae050
Authors: Victoria Zieschang In X Rebecca Elisabeth Beyer In X Maximilian Leo Müller In X Frederike Trautmann In X Titus Kühne In X Eike Nagel In X Andreas Rolf In X Andreas Schuster In X Grigorios Korosoglou In X Henning Steen In X Ali Yilmaz In X Steffen E Petersen In X Bjoern Andrew Remppis In X Gisela Thiede In X Anna Clara Nolden In X Sebastian Kelle In X
Abstract:

Aims

Extensive research has established cardiovascular magnetic resonance (CMR) as a powerful tool for diagnosing and monitoring various cardiovascular diseases (CVDs). However, CMR has yet to reach its full potential in routine clinical care, which is mainly due to reimbursement issues. Among other factors, overcoming this gap requires adequate awareness among healthcare professionals and potential patients, the extent of which is currently unknown. Therefore, we conducted a survey to assess awareness and identify knowledge gaps regarding the clinical role and socio-economic factors associated with CMR.

Methods and results

One hundred forty-four subjects not involved in direct patient care were enrolled at a German health conference and completed a 24-item survey, including procedural, clinical, and socio-economic questions about CMR. Respondents were well aware of the socio-economic impact of CVD. Common CMR indications were correctly identified by most participants, but only 22.9% knew the full spectrum. Participants underestimated the modality's benefits, such as absence of ionizing radiation and rare allergic reactions to contrast agents (only 70.9% and 37.6% correct answers, respectively). Respondents estimated the therapeutic guidance of CMR to be high (50.7% voted impact > 50%) and the annual demand to be increasing (89.9%). Attitudes towards CMR were generally positive, with 77.1% of participants willing to travel >25 km and 60.4% willing to pay >125 Euros to have a CMR examination.

Conclusion

Despite great interest in CMR, significant knowledge gaps hinder its optimal use in clinical practice. The development and implementation of awareness and education strategies are needed to realize the full clinical potential of CMR.
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Imaging for the diagnosis of acute myocarditis: can artificial intelligence improve diagnostic performance?

Open Access Issue N/A Vol 11 Published on 2024-01-01 PMID 39314764 PMCID PMC11417618
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Keywords: Artificial intelligence, Diagnosis, Myocarditis, Machine Learning, Cardiac Mri
DOI: https://doi.org/10.3389/fcvm.2024.1408574
Authors: Vijay Shyam-Sundar In X Daniel Harding In X Abbas Khan In X Musa Abdulkareem In X Greg Slabaugh In X Saidi A Mohiddin In X Steffen E Petersen In X Nay Aung In X
Abstract: Myocarditis is a cardiovascular disease characterised by inflammation of the heart muscle which can lead to heart failure. There is heterogeneity in the mode of presentation, underlying aetiologies, and clinical outcome with impact on a wide range of age groups which lead to diagnostic challenges. Cardiovascular magnetic resonance (CMR) is the preferred imaging modality in the diagnostic work-up of those with acute myocarditis. There is a need for systematic analytical approaches to improve diagnosis. Artificial intelligence (AI) and machine learning (ML) are increasingly used in CMR and has been shown to match human diagnostic performance in multiple disease categories. In this review article, we will describe the role of CMR in the diagnosis of acute myocarditis followed by a literature review on the applications of AI and ML to diagnose acute myocarditis. Only a few papers were identified with limitations in cases and control size and a lack of detail regarding cohort characteristics in addition to the absence of relevant cardiovascular disease controls. Furthermore, often CMR datasets did not include contemporary tissue characterisation parameters such as T1 and T2 mapping techniques, which are central to the diagnosis of acute myocarditis. Future work may include the use of explainability tools to enhance our confidence and understanding of the machine learning models with large, better characterised cohorts and clinical context improving the diagnosis of acute myocarditis.
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A review of evaluation approaches for explainable AI with applications in cardiology.

Open Access Issue 9 Vol 57 Published on 2024-01-01 PMID 39132011 PMCID PMC11315784
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Keywords: Cardiac, Evaluation, AI, Xai
DOI: https://doi.org/10.1007/s10462-024-10852-w
Authors: Ahmed M Salih In X Ilaria Boscolo Galazzo In X Polyxeni Gkontra In X Elisa Rauseo In X Aaron Mark Lee In X Karim Lekadir In X Petia Radeva In X Steffen E Petersen In X Gloria Menegaz In X
Abstract: Explainable artificial intelligence (XAI) elucidates the decision-making process of complex AI models and is important in building trust in model predictions. XAI explanations themselves require evaluation as to accuracy and reasonableness and in the context of use of the underlying AI model. This review details the evaluation of XAI in cardiac AI applications and has found that, of the studies examined, 37% evaluated XAI quality using literature results, 11% used clinicians as domain-experts, 11% used proxies or statistical analysis, with the remaining 43% not assessing the XAI used at all. We aim to inspire additional studies within healthcare, urging researchers not only to apply XAI methods but to systematically assess the resulting explanations, as a step towards developing trustworthy and safe models.

Supplementary information

The online version contains supplementary material available at 10.1007/s10462-024-10852-w.
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A history of cardiovascular magnetic resonance imaging in clinical practice and population science.

Open Access Issue N/A Vol 11 Published on 2024-01-01 PMID 38707888 PMCID PMC11066259
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Keywords: Nuclear magnetic resonance, Magnetic Resonance Imaging, History Of Medicine, Uk Biobank, Cardiovascular Magnetic Resonance (Cmr) Imaging, Multi-ethnic Study Of Atherosclerosis (Mesa)
DOI: https://doi.org/10.3389/fcvm.2024.1393896
Authors: Mihir M Sanghvi In X João A C Lima In X David A Bluemke In X Steffen E Petersen In X
Abstract: Cardiovascular magnetic resonance (CMR) imaging has become an invaluable clinical and research tool. Starting from the discovery of nuclear magnetic resonance, this article provides a brief overview of the key developments that have led to CMR as it is today, and how it became the modality of choice for large-scale population studies.
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Functional parcellation of the neonatal cortical surface.

Issue 2 Vol 34 Published on 2024-01-01 PMID 38372292 PMCID N/A
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Keywords: fMRI, Neonate, Functional Connectivity, Cortical Areas, Parcellation
DOI: https://doi.org/10.1093/cercor/bhae047
Authors: Michael J Myers In X Alyssa K Labonte In X Evan M Gordon In X Timothy O Laumann In X Jiaxin C Tu In X Muriah D Wheelock In X Ashley N Nielsen In X Rebecca F Schwarzlose In X M Catalina Camacho In X Dimitrios Alexopoulos In X Barbara B Warner In X Nandini Raghuraman In X Joan L Luby In X Deanna M Barch In X Damien A Fair In X Steven E Petersen In X Cynthia E Rogers In X Christopher D Smyser In X Chad M Sylvester In X
Abstract: The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.
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NHS Health Check attendance is associated with reduced multiorgan disease risk: a matched cohort study in the UK Biobank.

Open Access Issue 1 Vol 22 Published on 2024-01-01 PMID 38254067 PMCID PMC10804500
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Keywords: Public Health, Preventive Medicine, Primary Care, General Medicine, Nhs Health Check
DOI: https://doi.org/10.1186/s12916-023-03187-w
Authors: Celeste McCracken In X Zahra Raisi-Estabragh In X Liliana Szabo In X John Robson In X Betty Raman In X Anya Topiwala In X Adriana Roca-Fernández In X Masud Husain In X Steffen E Petersen In X Stefan Neubauer In X Thomas E Nichols In X
Abstract:

Background

The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not.

Methods

Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke, dementia, myocardial infarction, atrial fibrillation, heart failure, fatty liver disease, alcoholic liver disease, liver cirrhosis, liver failure, acute kidney injury, chronic kidney disease (stage 3 +), cardiovascular mortality, and all-cause mortality. Time-varying survival modelling was used to compare adjusted outcome rates between the groups.

Results

In the immediate 2 years after the NHS Health Check, higher diagnosis rates were observed for hypertension, high cholesterol, and chronic kidney disease among health check recipients compared to their matched counterparts. However, in the longer term, NHS Health Check recipients had significantly lower risk across all multiorgan disease outcomes and reduced rates of cardiovascular and all-cause mortality.

Conclusions

The NHS Health Check is linked to reduced incidence of disease across multiple organ systems, which may be attributed to risk modification through earlier detection and treatment of key risk factors such as hypertension and high cholesterol. This work adds important evidence to the growing body of research supporting the effectiveness of preventative interventions in reducing longer-term multimorbidity.
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Blood biomarkers to detect functional impairment in adult patients with repaired tetralogy of Fallot.

Open Access Issue N/A Vol 14 Published on 2023-12-01 PMID 39712984 PMCID PMC11657782
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Keywords:
DOI: https://doi.org/10.1016/j.ijcchd.2023.100483
Authors: S Alborikan In X A Althunayyan In X B Pandya In X K Von Klemperer In X F Walker In X S Cullen In X A Bhan In X S Badiani In X D Encarnacion In X R Monteiro In X S E Petersen In X S Bhattacharyya In X G Lloyd In X
Abstract:

Background

The relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF).

Methods

Peripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test.

Results

The mean value of NT-proBNP was 160 ± 137 pg/ml, and sST2 was 29 ± 13, ng/ml in the entire population. 58 % had an elevated NT-proBNP, while sST2 was abnormal in 40 %. Mean NT-proBNP was significantly higher in patients with severe PR (169 ± 150 vs145 ± 118, pg/ml, p < 0.001), while similar sST2 levels were observed in both groups (29 ± 14 vs30 ± 12, ng/ml, p > 0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention (174 ± 145 vs 107 ± 100, pg/ml, p < 0.001); (31 ± 13 vs 29 ± 15, ng/ml, p < 0.05). Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r = -0.60, p < 0.001) was stronger. The optimal cut-off of 90 pg/ml for NT-proBNP had a sensitivity of 74 % and specificity of 63 % for detection of impaired exercise capacity.

Conclusions

Serum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch repair. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.
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Using machine learning to enhance prediction of atrial fibrillation recurrence after catheter ablation.

Open Access Issue 6 Vol 39 Published on 2023-12-01 PMID 38045451 PMCID PMC10692862
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Keywords: Atrial fibrillation, Catheter ablation, Cardiac Computed Tomography, Machine Learning, Left Atrium
DOI: https://doi.org/10.1002/joa3.12927
Authors: Mark S Brahier In X Fengwei Zou In X Musa Abdulkareem In X Shwetha Kochi In X Frank Migliarese In X Athanasios Thomaides In X Xiaoyang Ma In X Colin Wu In X Veit Sandfort In X Peter J Bergquist In X Monvadi B Srichai In X Jonathan P Piccini In X Steffen E Petersen In X Jose D Vargas In X
Abstract:

Background

Traditional risk scores for recurrent atrial fibrillation (AF) following catheter ablation utilize readily available clinical and echocardiographic variables and yet have limited discriminatory capacity. Use of data from cardiac imaging and deep learning may help improve accuracy and prediction of recurrent AF after ablation.

Methods

We evaluated patients with symptomatic, drug-refractory AF undergoing catheter ablation. All patients underwent pre-ablation cardiac computed tomography (cCT). LAVi was computed using a deep-learning algorithm. In a two-step analysis, random survival forest (RSF) was used to generate prognostic models with variables of highest importance, followed by Cox proportional hazard regression analysis of the selected variables. Events of interest included early and late recurrence.

Results

Among 653 patients undergoing AF ablation, the most important factors associated with late recurrence by RSF analysis at 24 (+/-18) months follow-up included LAVi and early recurrence. In total, 5 covariates were identified as independent predictors of late recurrence: LAVi (HR per mL/m2 1.01 [1.01-1.02]; p < .001), early recurrence (HR 2.42 [1.90-3.09]; p < .001), statin use (HR 1.38 [1.09-1.75]; p = .007), beta-blocker use (HR 1.29 [1.01-1.65]; p = .043), and adjunctive cavotricuspid isthmus ablation [HR 0.74 (0.57-0.96); p = .02]. Survival analysis demonstrated that patients with both LAVi >66.7 mL/m2 and early recurrence had the highest risk of late recurrence risk compared with those with LAVi <66.7 mL/m2 and no early recurrence (HR 4.52 [3.36-6.08], p < .001).

Conclusions

Machine learning-derived, full volumetric LAVi from cCT is the most important pre-procedural risk factor for late AF recurrence following catheter ablation. The combination of increased LAVi and early recurrence confers more than a four-fold increased risk of late recurrence.
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Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects.

Open Access Issue 24 Vol 148 Published on 2023-12-01 PMID 37855144 PMCID PMC10712993
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Keywords: Cardiovascular diseases, Electrocardiography, Mortality, Exercise, Ventricular Premature Complexes
DOI: https://doi.org/10.1161/circulationaha.123.064633
Authors: Stefan van Duijvenboden In X Julia Ramírez In X Michele Orini In X Nay Aung In X Steffen E Petersen In X Aiden Doherty In X Andrew Tinker In X Patricia B Munroe In X Pier D Lambiase In X
Abstract:

Background

The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality.

Methods

A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy.

Results

Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1-5 exercise PVCs, P<0.001) and HR, 1.3 (1-5 recovery PVCs, P<0.001). Risks were higher with increasing PVC count: HR, 1.8 (>20 exercise PVCs, P<0.001) and HR, 1.6 (>5 recovery PVCs, P<0.001). A similar trend was observed for all-cause mortality, although associations were only significant for high PVC burdens: HRs, 1.6 (>20 exercise PVCs, P<0.001) and 1.5 (>5 recovery PVCs, P<0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs.

Conclusions

In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy.
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Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC.

Open Access Issue 45 Vol 44 Published on 2023-12-01 PMID 37622660 PMCID PMC10691193
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Keywords: Echocardiography, Nuclear Cardiology, Cardiac Computed Tomography, Cardiovascular Magnetic Resonance, Competency-based Cardiac Imaging
DOI: https://doi.org/10.1093/eurheartj/ehad578
Authors: Mark Westwood In X Ana G Almeida In X Emanuele Barbato In X Victoria Delgado In X Santo Dellegrottaglie In X Kevin F Fox In X Luna Gargani In X Kurt Huber In X Pál Maurovich-Horvat In X Jose L Merino In X Richard Mindham In X Denisa Muraru In X Lis Neubeck In X Robin Nijveldt In X Michael Papadakis In X Gianluca Pontone In X Susanna Price In X Giuseppe M C Rosano In X Alexia Rossi In X Leyla Elif Sade In X Jeanette Schulz-Menger In X Franz Weidinger In X Stephan Achenbach In X Steffen E Petersen In X
Abstract: Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
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Diagnostic performance of clinical likelihood models of obstructive coronary artery disease to predict myocardial perfusion defects.

Issue 1 Vol 25 Published on 2023-12-01 PMID 37282714 PMCID N/A
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Keywords: coronary artery disease, myocardial perfusion imaging, Coronary Computed Tomography Angiography, Chronic Coronary Syndrome, Clinical Likelihood
DOI: https://doi.org/10.1093/ehjci/jead135
Authors: Laust Dupont Rasmussen In X Line Emilie Brøgger Albertsen In X Louise Nissen In X June Anita Ejlersen In X Christin Isaksen In X Theodore Murphy In X Hanne Maare Søndergaard In X Jane Kirk In X Lau Brix In X Lars Christian Gormsen In X Steffen E Petersen In X Morten Bøttcher In X Simon Winther In X
Abstract:

Aims

Clinical likelihood (CL) models are designed based on a reference of coronary stenosis in patients with suspected obstructive coronary artery disease. However, a reference standard for myocardial perfusion defects (MPDs) could be more appropriate. We aimed to investigate the ability of the 2019 European Society of Cardiology pre-test probability (ESC-PTP), the risk-factor-weighted (RF-CL) model, and coronary artery calcium score-weighted (CACS-CL) model to diagnose MPDs.

Methods and results

Symptomatic stable de novo chest pain patients (n = 3374) underwent coronary computed tomography angiography and subsequent myocardial perfusion imaging by single-photon emission computed tomography, positron emission tomography, or cardiac magnetic resonance. For all modalities, MPD was defined as coronary computed tomography angiography with suspected stenosis and stress-perfusion abnormality in ≥2 segments. The ESC-PTP was calculated based on age, sex, and symptom typicality, and the RF-CL and CACS-CL additionally included a number of risk factors and CACS. In total, 219/3374 (6.5%) patients had an MPD. Both the RF-CL and the CACS-CL classified substantially more patients to low CL (<5%) of obstructive coronary artery disease compared with the ESC-PTP (32.5 and 54.1 vs. 12.0%, P < 0.001) with preserved low prevalences of MPD (<2% for all models). Compared with the ESC-PTP [area under the receiver-operating characteristic curve (AUC) 0.74 (0.71-0.78)], the discrimination of having an MPD was higher for the CACS-CL model [AUC 0.88 (0.86-0.91), P < 0.001], while it was similar for the RF-CL model [AUC 0.73 (0.70-0.76), P = 0.32].

Conclusion

Compared with basic CL models, the RF-CL and CACS-CL models improve down classification of patients to a very low-risk group with a low prevalence of MPD.
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Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.

Open Access Issue 6 Vol 58 Published on 2023-12-01 PMID 36929232 PMCID PMC10947470
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Keywords: Aging, Cardiac Imaging, Cardiac Health, Radiomics
DOI: https://doi.org/10.1002/jmri.28675
Authors: Ahmed M Salih In X Esmeralda Ruiz Pujadas In X Víctor M Campello In X Celeste McCracken In X Nicholas C Harvey In X Stefan Neubauer In X Karim Lekadir In X Thomas E Nichols In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4).

Field strength/sequence

A 1.5 T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The "age gap" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49).

Statistical test

Multiple testing correction with false discovery method (threshold = 5%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, "disinterested" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.
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Genome-Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants.

Open Access Issue 21 Vol 12 Published on 2023-11-01 PMID 37889180 PMCID PMC10727393
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Keywords: Cardiovascular disease, Pericardial Adipose Tissue, Genome‐wide Association Study
DOI: https://doi.org/10.1161/jaha.123.030661
Authors: Ahmed Salih In X Maddalena Ardissino In X Aaron Z Wagen In X Andrew Bard In X Liliana Szabo In X Mina Ryten In X Steffen E Petersen In X André Altmann In X Zahra Raisi-Estabragh In X
Abstract: BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independent of general or subcutaneous adiposity. We characterize the genetic architecture of adiposity-adjusted PAT and identify causal associations between PAT and adverse cardiac magnetic resonance imaging measures of cardiac structure and function in 28 161 UK Biobank participants. METHODS AND RESULTS The PAT phenotype was extracted from cardiac magnetic resonance images using an automated image analysis tool previously developed and validated in this cohort. A genome-wide association study was performed with PAT area set as the phenotype, adjusting for age, sex, and other measures of obesity. Functional mapping and Bayesian colocalization were used to understand the biologic role of identified variants. Mendelian randomization analysis was used to examine potential causal links between genetically determined PAT and cardiac magnetic resonance-derived measures of left ventricular structure and function. We discovered 12 genome-wide significant variants, with 2 independent sentinel variants (rs6428792, P=4.20×10-9 and rs11992444, P=1.30×10-12) at 2 distinct genomic loci, that were mapped to 3 potentially causal genes: T-box transcription factor 15 (TBX15), tryptophanyl tRNA synthetase 2, mitochondrial (WARS2) and early B-cell factor-2 (EBF2) through functional annotation. Bayesian colocalization additionally suggested a role of RP4-712E4.1. Genetically predicted differences in adiposity-adjusted PAT were causally associated with adverse left ventricular remodeling. CONCLUSIONS This study provides insights into the genetic architecture determining differential PAT deposition, identifies causal links with left structural and functional parameters, and provides novel data about the pathophysiological importance of adiposity distribution.
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Plan robustness evaluation strategies in whole-pelvic proton therapy for high-risk prostate cancer patients within a randomised clinical trial.

Issue 11 Vol 62 Published on 2023-11-01 PMID 37773941 PMCID N/A
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Keywords: prostate cancer, Clinical Trial, Proton Therapy, Robust Evaluation
DOI: https://doi.org/10.1080/0284186x.2023.2261621
Authors: Sofie Tilbæk In X Stine Elleberg Petersen In X Liliana Stolarczyk In X Anne Vestergaard In X Heidi S Rønde In X Lise N Bentzen In X Jimmi Søndergaard In X Morten Høyer In X Ludvig Paul Muren In X
Abstract:

Background

Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints.

Material and methods

Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE.

Results

Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively.

Conclusion

The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage.
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The year 2022 in the European Heart Journal-Cardiovascular Imaging: Part I.

Issue 12 Vol 24 Published on 2023-11-01 PMID 37738411 PMCID N/A
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Keywords: Congenital heart disease, Cardiomyopathy, Heart Failure, Valvular Heart Disease, Cardiac Imaging
DOI: https://doi.org/10.1093/ehjci/jead237
Authors: Steffen E Petersen In X Denisa Muraru In X Mark Westwood In X Marc R Dweck In X Giovanni Di Salvo In X Victoria Delgado In X Bernard Cosyns In X
Abstract: The European Heart Journal-Cardiovascular Imaging with its over 10 years existence is an established leading multi-modality cardiovascular imaging journal. Pertinent publications including original research, how-to papers, reviews, consensus documents, and in our journal from 2022 have been highlighted in two reports. Part I focuses on cardiomyopathies, heart failure, valvular heart disease, and congenital heart disease and related emerging techniques and technologies.
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Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.

Issue 5 Vol 79 Published on 2023-11-01 PMID 37348789 PMCID N/A
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Keywords: Cardiac, MRI, Imaging, Hepatic, Heart Failure, liver disease, Cvd, Nafld, Atrial Fibrilliation
DOI: https://doi.org/10.1016/j.jhep.2023.05.046
Authors: Adriana Roca-Fernandez In X Rajarshi Banerjee In X Helena Thomaides-Brears In X Alison Telford In X Arun Sanyal In X Stefan Neubauer In X Thomas E Nichols In X Betty Raman In X Celeste McCracken In X Steffen E Petersen In X Ntobeko Ab Ntusi In X Daniel J Cuthbertson In X Michele Lai In X Andrea Dennis In X Amitava Banerjee In X
Abstract:

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.
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An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.

Open Access Issue 5 Vol 4 Published on 2023-10-01 PMID 37794871 PMCID PMC10545512
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Keywords: Artificial intelligence, Quality control, Cardiac function, Cardiac Segmentation, Cardiac Magnetic Resonance
DOI: https://doi.org/10.1093/ehjdh/ztad044
Authors: Jorge Mariscal-Harana In X Clint Asher In X Vittoria Vergani In X Maleeha Rizvi In X Louise Keehn In X Raymond J Kim In X Robert M Judd In X Steffen E Petersen In X Reza Razavi In X Andrew P King In X Bram Ruijsink In X Esther Puyol-Antón In X
Abstract:

Aims

Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.

Methods and results

Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (n = 414) and five external datasets (n = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.

Conclusion

We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.
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2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes.

Issue 39 Vol 44 Published on 2023-10-01 PMID 37622663 PMCID N/A
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Keywords: Diabetes mellitus, Prevention, Atrial fibrillation, Guidelines, Cardiovascular disease, Arrhythmias, Heart Failure, Cardiovascular Risk Assessment, Pharmacological Treatment, Patient-centred Care, Aortic And Peripheral Arterial Diseases, coronary artery disease, risk factors, Chronic Kidney Disease
DOI: https://doi.org/10.1093/eurheartj/ehad192
Authors: Nikolaus Marx In X Massimo Federici In X Katharina Schütt In X Dirk Müller-Wieland In X Ramzi A Ajjan In X Manuel J Antunes In X Ruxandra M Christodorescu In X Carolyn Crawford In X Emanuele Di Angelantonio In X Björn Eliasson In X Christine Espinola-Klein In X Laurent Fauchier In X Martin Halle In X William G Herrington In X Alexandra Kautzky-Willer In X Ekaterini Lambrinou In X Maciej Lesiak In X Maddalena Lettino In X Darren K McGuire In X Wilfried Mullens In X Bianca Rocca In X Naveed Sattar In X In X
Abstract: No Abstract Available
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Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC.

Open Access Issue 11 Vol 24 Published on 2023-10-01 PMID 37622662 PMCID PMC10610731
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Keywords: Echocardiography, Nuclear Cardiology, Cardiac Computed Tomography, Cardiovascular Magnetic Resonance, Competency-based Cardiac Imaging
DOI: https://doi.org/10.1093/ehjci/jead216
Authors: Mark Westwood In X Ana G Almeida In X Emanuele Barbato In X Victoria Delgado In X Santo Dellegrottaglie In X Kevin F Fox In X Luna Gargani In X Kurt Huber In X Pál Maurovich-Horvat In X Jose L Merino In X Richard Mindham In X Denisa Muraru In X Lis Neubeck In X Robin Nijveldt In X Michael Papadakis In X Gianluca Pontone In X Susanna Price In X Giuseppe M C Rosano In X Alexia Rossi In X Leyla Elif Sade In X Jeanette Schulz-Menger In X Franz Weidinger In X Stephan Achenbach In X Steffen E Petersen In X
Abstract: Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
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2023 ESC Guidelines for the management of acute coronary syndromes.

Issue 38 Vol 44 Published on 2023-10-01 PMID 37622654 PMCID N/A
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Keywords: Fibrinolysis, Myocardial infarction, Unstable angina, Revascularization, Percutaneous coronary intervention, acute coronary syndrome, Recommendations, Secondary Prevention, Guidelines, Reperfusion Therapy, Antithrombotic Therapy, Patient-centred Care, St-segment Elevation Myocardial Infarction, Non-st-elevation Myocardial Infarction, Invasive Strategy, High-sensitivity Troponin, Acute Cardiac Care, Minoca
DOI: https://doi.org/10.1093/eurheartj/ehad191
Authors: Robert A Byrne In X Xavier Rossello In X J J Coughlan In X Emanuele Barbato In X Colin Berry In X Alaide Chieffo In X Marc J Claeys In X Gheorghe-Andrei Dan In X Marc R Dweck In X Mary Galbraith In X Martine Gilard In X Lynne Hinterbuchner In X Ewa A Jankowska In X Peter Jüni In X Takeshi Kimura In X Vijay Kunadian In X Margret Leosdottir In X Roberto Lorusso In X Roberto F E Pedretti In X Angelos G Rigopoulos In X Maria Rubini Gimenez In X Holger Thiele In X Pascal Vranckx In X Sven Wassmann In X Nanette Kass Wenger In X Borja Ibanez In X In X
Abstract: No Abstract Available
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Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity.

Open Access Issue N/A Vol 279 Published on 2023-10-01 PMID 37557971 PMCID PMC10528723
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Keywords: fMRI, decision-making, emotion, Ambiguity, Cingulo-opercular Network
DOI: https://doi.org/10.1016/j.neuroimage.2023.120314
Authors: Jordan E Pierce In X Nathan M Petro In X Elizabeth Clancy In X Caterina Gratton In X Steven E Petersen In X Maital Neta In X
Abstract: Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.
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Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.

Open Access Issue 11 Vol 24 Published on 2023-10-01 PMID 37440761 PMCID PMC10610755
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Keywords: Cardiac function, Cardiac morphology, Mental health, Cardiovascular Magnetic Resonance, Neuroticism, Cardiovascular Remodelling
DOI: https://doi.org/10.1093/ehjci/jead166
Authors: Adil Mahmood In X Judit Simon In X Jackie Cooper In X Theodore Murphy In X Celeste McCracken In X Juan Quiroz In X Liliana Laranjo In X Nay Aung In X Aaron Mark Lee In X Mohammed Y Khanji In X Stefan Neubauer In X Zahra Raisi-Estabragh In X Pal Maurovich-Horvat In X Steffen E Petersen In X
Abstract:

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.
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Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC.

Open Access Issue 2 Vol 1 Published on 2023-09-01 PMID 39045068 PMCID PMC11195717
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Keywords: Echocardiography, Nuclear Cardiology, Cardiac Computed Tomography, Cardiovascular Magnetic Resonance, Competency-based Cardiac Imaging
DOI: https://doi.org/10.1093/ehjimp/qyad023
Authors: Mark Westwood In X Ana G Almeida In X Emanuele Barbato In X Victoria Delgado In X Santo Dellegrottaglie In X Kevin F Fox In X Luna Gargani In X Kurt Huber In X Pál Maurovich-Horvat In X Jose L Merino In X Richard Mindham In X Denisa Muraru In X Lis Neubeck In X Robin Nijveldt In X Michael Papadakis In X Gianluca Pontone In X Susanna Price In X Giuseppe M C Rosano In X Alexia Rossi In X Leyla Elif Sade In X Jeanette Schulz-Menger In X Franz Weidinger In X Stephan Achenbach In X Steffen E Petersen In X
Abstract: Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
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Association between subclinical atherosclerosis and cardiac structure and function-results from the UK Biobank Study.

Open Access Issue 2 Vol 1 Published on 2023-09-01 PMID 37822973 PMCID PMC10563379
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Keywords: MRI, Heart Failure, Carotid, Cardiac Structure And Function
DOI: https://doi.org/10.1093/ehjimp/qyad010
Authors: Judit Simon In X Kenneth Fung In X Zahra Raisi-Estabragh In X Nay Aung In X Mohammed Y Khanji In X Emese Zsarnóczay In X Béla Merkely In X Patricia B Munroe In X Nicholas C Harvey In X Stefan K Piechnik In X Stefan Neubauer In X Paul Leeson In X Steffen E Petersen In X Pál Maurovich-Horvat In X
Abstract:

Aims

Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease.

Methods and results

Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals (61.6 ± 7.5 years, 45.9% male) were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all P < 0.05).

Conclusion

Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.
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Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.

Open Access Issue 10 Vol 24 Published on 2023-09-01 PMID 37699069 PMCID PMC10531121
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Keywords: Prognosis, Cardiovascular events, Risk stratification, Heart Failure, Cardiovascular Magnetic Resonance, Left Ventricular Systolic Dysfunction
DOI: https://doi.org/10.1093/ehjci/jead218
Authors: Elisa Rauseo In X Musa Abdulkareem In X Abbas Khan In X Jackie Cooper In X Aaron M Lee In X Nay Aung In X Gregory G Slabaugh In X Steffen E Petersen In X
Abstract:

Aims

Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.

Methods and results

Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.

Conclusions

Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.
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Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.

Open Access Issue 9 Vol 8 Published on 2023-09-01 PMID 37494011 PMCID PMC10372756
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Keywords:
DOI: https://doi.org/10.1001/jamacardio.2023.2167
Authors: Nay Aung In X Qingning Wang In X Stefan van Duijvenboden In X Richard Burns In X Svetlana Stoma In X Zahra Raisi-Estabragh In X Selda Ahmet In X Elias Allara In X Angela Wood In X Emanuele Di Angelantonio In X John Danesh In X Patricia B Munroe In X Alistair Young In X Nicholas C Harvey In X Veryan Codd In X Christopher P Nelson In X Steffen E Petersen In X Nilesh J Samani In X
Abstract:

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.
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Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.

Open Access Issue 10 Vol 24 Published on 2023-09-01 PMID 37309807 PMCID PMC10531143
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Keywords: Ethnicity, Cardiovascular Magnetic Resonance, Population Health, Women’s Health, Antihypertensive Therapies
DOI: https://doi.org/10.1093/ehjci/jead123
Authors: Hussein Elghazaly In X Celeste McCracken In X Liliana Szabo In X James Malcolmson In X Charlotte H Manisty In X Alun H Davies In X Stefan K Piechnik In X Nicholas C Harvey In X Stefan Neubauer In X Saidi A Mohiddin In X Steffen E Petersen In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Aims

To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.

Methods and results

We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.

Conclusion

Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.
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PROTEUS Study: A Prospective Randomized Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

Issue N/A Vol 263 Published on 2023-09-01 PMID 37192698 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.ahj.2023.05.003
Authors: Gary Woodward In X Mamta Bajre In X Sanjeev Bhattacharyya In X Maria Breen In X Virginia Chiocchia In X Helen Dawes In X Hakim-Moulay Dehbi In X Tine Descamps In X Elena Frangou In X Carol-Ann Fazakarley In X Victoria Harris In X Will Hawkes In X Oliver Hewer In X Casey L Johnson In X Samuel Krasner In X Lynn Laidlaw In X Jonathan Lau In X Tom Marwick In X Steffen E Petersen In X Hania Piotrowska In X Ged Ridgeway In X David P Ripley In X Emily Sanderson In X Natalie Savage In X Rizwan Sarwar In X Louise Tetlow In X Ben Thompson In X Samantha Thulborn In X Victoria Williamson In X William Woodward In X Ross Upton In X Paul Leeson In X
Abstract:

Background

Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome.

Methods

PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis.

Discussion

This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE.

Trial registration

Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.
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Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.

Open Access Issue 4 Vol 4 Published on 2023-08-01 PMID 37538142 PMCID PMC10393938
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Keywords: Electrocardiogram, Left ventricular hypertrophy, Cardiovascular Screening, Machine Learning, Cardiovascular Magnetic Resonance Imaging
DOI: https://doi.org/10.1093/ehjdh/ztad037
Authors: Hafiz Naderi In X Julia Ramírez In X Stefan van Duijvenboden In X Esmeralda Ruiz Pujadas In X Nay Aung In X Lin Wang In X Choudhary Anwar Ahmed Chahal In X Karim Lekadir In X Steffen E Petersen In X Patricia B Munroe In X
Abstract:

Aims

Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification.

Methods and results

We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (P < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models.

Conclusion

A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.
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Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.

Issue N/A Vol 201 Published on 2023-08-01 PMID 37348153 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.amjcard.2023.05.039
Authors: Aeshah Althunayyan In X Sahar Alborikan In X Sveeta Badiani In X Kit Wong In X Rakesh Uppal In X Nikhil Patel In X Steffen E Petersen In X Guy Lloyd In X Sanjeev Bhattacharyya In X
Abstract: The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.
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Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.

Issue 9 Vol 24 Published on 2023-08-01 PMID 37140153 PMCID N/A
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Keywords: Surgery, Mitral regurgitation, Mitral Valve Prolapse, Global Longitudinal Strain, Lv Volumes
DOI: https://doi.org/10.1093/ehjci/jead093
Authors: Aeshah M Althunayyan In X Sahar Alborikan In X Sveeta Badiani In X Kit Wong In X Rakesh Uppal In X Nikhil Patel In X Steffen E Petersen In X Guy Lloyd In X Sanjeev Bhattacharyya In X
Abstract:

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.
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Interchangeability in Left Ventricular Ejection Fraction Measured by Echocardiography and cardiovascular Magnetic Resonance: Not a Perfect Match in the Real World.

Issue 8 Vol 48 Published on 2023-08-01 PMID 37001574 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.cpcardiol.2023.101721
Authors: Joseph Clark In X Adrian Ionescu In X C Anwar A Chahal In X Sanjeev Bhattacharyya In X Guy Lloyd In X Kristian Galanti In X Sabina Gallina In X Jun Hua Chong In X Steffen E Petersen In X Fabrizio Ricci In X Mohammed Y Khanji In X
Abstract: Comparisons of transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) derived left ventricular ejection fraction (LVEF) have been reported in core-lab settings but are limited in the real-world setting. We retrospectively identified outpatients from 4 hospital sites who had clinically indicated quantitative assessment of LVEFTTE and LVEFCMR and evaluated their concordance. In 767 patients (mean age 47.6 years; 67.9% males) the median inter-modality interval was 35 days. There was significant positive correlation between the 2 modalities (r = 0.75; P < 0.001). Median LVEF was 54% (IQR 47%, 60%) for TTE and 59% (IQR 51%, 64%) for CMR, (P < 0.001). Normal LVEFTTE was confirmed by CMR in 90.6% of cases. Of patients with severely impaired LVEFTTE, 42.3% were upwardly reclassified by CMR as less severely impaired. The overall proportion of patients that had their LVEF category confirmed by both imaging modalities was 64.4%; Cohen's Kappa 0.41, indicating fair-to-moderate agreement. Overall, CMR upwardly reclassified 28% of patients using the British Society of Echocardiography LVEF grading, 18.6% using the European Society of Cardiology heart failure classification, and 29.6% using specific reference ranges for each modality. In a multi-site "real-worldˮ clinical setting, there was significant discrepancy between LVEFTTE and LVEFCMR measurement. Only 64.4% had their LVEF category confirmed by both imaging modalities. LVEFTTE was generally lower than LVEFCMR. LVEFCMR upwardly reclassified almost half of patients with severe LV dysfunction by LVEFTTE. Clinicians should consider the inter-modality variation before making therapeutic recommendations, particularly as clinical trial LVEF thresholds have historically been guided by echocardiography.
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Proton therapy planning and image-guidance strategies within a randomized controlled trial for high-risk prostate cancer.

Open Access Issue N/A Vol 41 Published on 2023-07-01 PMID 37441541 PMCID PMC10334116
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Keywords: prostate cancer, High-risk, Proton Therapy, Randomized Trial
DOI: https://doi.org/10.1016/j.ctro.2023.100632
Authors: Sofie Tilbæk In X Ludvig Paul Muren In X Anne Vestergaard In X Liliana Stolarczyk In X Heidi S Rønde In X Tanja S Johansen In X Jimmi Søndergaard In X Morten Høyer In X Jan Alsner In X Lise Nørgaard Bentzen In X Stine Elleberg Petersen In X
Abstract: The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the trial.
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Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure.

Open Access Issue 1 Vol 14 Published on 2023-07-01 PMID 37429843 PMCID PMC10333277
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Keywords:
DOI: https://doi.org/10.1038/s41467-023-39253-3
Authors: Danielle Rasooly In X Gina M Peloso In X Alexandre C Pereira In X Hesam Dashti In X Claudia Giambartolomei In X Eleanor Wheeler In X Nay Aung In X Brian R Ferolito In X Maik Pietzner In X Eric H Farber-Eger In X Quinn Stanton Wells In X Nicole M Kosik In X Liam Gaziano In X Daniel C Posner In X A Patrícia Bento In X Qin Hui In X Chang Liu In X Krishna Aragam In X Zeyuan Wang In X Brian Charest In X Jennifer E Huffman In X Peter W F Wilson In X Lawrence S Phillips In X John Whittaker In X Patricia B Munroe In X Steffen E Petersen In X Kelly Cho In X Andrew R Leach In X María Paula Magariños In X John Michael Gaziano In X In X Claudia Langenberg In X Yan V Sun In X Jacob Joseph In X Juan P Casas In X
Abstract: We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.
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Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.

Open Access Issue 7 Vol 16 Published on 2023-07-01 PMID 37407123 PMCID PMC10317841
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Keywords: brain aging, ischemic heart disease, Cognitive Decline, Vascular Risk Factors, Brain Health
DOI: https://doi.org/10.1016/j.jcmg.2023.01.016
Authors: Elisa Rauseo In X Ahmed Salih In X Zahra Raisi-Estabragh In X Nay Aung In X Neha Khanderia In X Gregory G Slabaugh In X Charles R Marshall In X Stefan Neubauer In X Petia Radeva In X Ilaria Boscolo Galazzo In X Gloria Menegaz In X Steffen E Petersen In X
Abstract:

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.
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Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.

Issue 7 Vol 8 Published on 2023-07-01 PMID 37285143 PMCID PMC10248816
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Keywords:
DOI: https://doi.org/10.1001/jamacardio.2023.1290
Authors: Fabrizio Ricci In X Mohammed Y Khanji In X Giandomenico Bisaccia In X Alberto Cipriani In X Annamaria Di Cesare In X Laura Ceriello In X Cesare Mantini In X Marco Zimarino In X Artur Fedorowski In X Sabina Gallina In X Steffen E Petersen In X Chiara Bucciarelli-Ducci In X
Abstract:

Importance

The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown.

Objective

To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain.

Data sources

PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021.

Study selection

Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included.

Data extraction and synthesis

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Main outcomes and measures

Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death.

Results

A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%.

Conclusion and relevance

In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.
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Deep Learning Segmentation of the Right Ventricle in Cardiac MRI: The M&Ms Challenge.

Issue 7 Vol 27 Published on 2023-07-01 PMID 37067963 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1109/jbhi.2023.3267857
Authors: Carlos Martin-Isla In X Victor M Campello In X Cristian Izquierdo In X Kaisar Kushibar In X Carla Sendra-Balcells In X Polyxeni Gkontra In X Alireza Sojoudi In X Mitchell J Fulton In X Tewodros Weldebirhan Arega In X Kumaradevan Punithakumar In X Lei Li In X Xiaowu Sun In X Yasmina Al Khalil In X Di Liu In X Sana Jabbar In X Sandro Queiros In X Francesco Galati In X Moona Mazher In X Zheyao Gao In X Marcel Beetz In X Lennart Tautz In X Christoforos Galazis In X Marta Varela In X Markus Hullebrand In X Vicente Grau In X Xiahai Zhuang In X Domenec Puig In X Maria A Zuluaga In X Hassan Mohy-Ud-Din In X Dimitris Metaxas In X Marcel Breeuwer In X Rob J van der Geest In X Michelle Noga In X Stephanie Bricq In X Mark E Rentschler In X Andrea Guala In X Steffen E Petersen In X Sergio Escalera In X Jose F Rodriguez Palomares In X Karim Lekadir In X
Abstract: In recent years, several deep learning models have been proposed to accurately quantify and diagnose cardiac pathologies. These automated tools heavily rely on the accurate segmentation of cardiac structures in MRI images. However, segmentation of the right ventricle is challenging due to its highly complex shape and ill-defined borders. Hence, there is a need for new methods to handle such structure's geometrical and textural complexities, notably in the presence of pathologies such as Dilated Right Ventricle, Tricuspid Regurgitation, Arrhythmogenesis, Tetralogy of Fallot, and Inter-atrial Communication. The last MICCAI challenge on right ventricle segmentation was held in 2012 and included only 48 cases from a single clinical center. As part of the 12th Workshop on Statistical Atlases and Computational Models of the Heart (STACOM 2021), the M&Ms-2 challenge was organized to promote the interest of the research community around right ventricle segmentation in multi-disease, multi-view, and multi-center cardiac MRI. Three hundred sixty CMR cases, including short-axis and long-axis 4-chamber views, were collected from three Spanish hospitals using nine different scanners from three different vendors, and included a diverse set of right and left ventricle pathologies. The solutions provided by the participants show that nnU-Net achieved the best results overall. However, multi-view approaches were able to capture additional information, highlighting the need to integrate multiple cardiac diseases, views, scanners, and acquisition protocols to produce reliable automatic cardiac segmentation algorithms.
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Impact of Sleep Duration and Chronotype on Cardiac Structure and Function: The UK Biobank Study.

Issue 7 Vol 48 Published on 2023-07-01 PMID 36906161 PMCID N/A
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DOI: https://doi.org/10.1016/j.cpcardiol.2023.101688
Authors: Mohammed Y Khanji In X Shahid Karim In X Jackie Cooper In X Anwar Chahal In X Nay Aung In X Virend K Somers In X Stefan Neubauer In X Steffen E Petersen In X
Abstract: Sleep duration and chronotype have been associated with increased morbidity and mortality. We assessed for associations between sleep duration and chronotype on cardiac structure and function. UK Biobank participants with CMR data and without known cardiovascular disease were included. Self-reported sleep duration was categorized as short (<7 h/d), normal (7-9 h/d) and long (>9 h/d). Self-reported chronotype was categories as "definitely morning" or "definitely evening." Analysis included 3903 middle-aged adults: 929 short, 2924 normal and 50 long sleepers; with 966 definitely-morning and 355 definitely-evening chronotypes. Long sleep was independently associated with lower left ventricular (LV) mass (-4.8%, P = 0.035), left atrial maximum volume (-8.1%, P = 0.041) and right ventricular (RV) end-diastolic volume (-4.8%, P = 0.038) compared to those with normal sleep duration. Evening chronotype was independently associated with lower LV end-diastolic volume (-2.4%, P = 0.021), RV end-diastolic volume (-3.6%, P = 0.0006), RV end systolic volume (-5.1%, P = 0.0009), RV stroke volume (RVSV -2.7%, P = 0.033), right atrial maximal volume (-4.3%, P = 0.011) and emptying fraction (+1.3%, P = 0.047) compared to morning chronotype. Sex interactions existed for sleep duration and chronotype and age interaction for chronotype even after considering potential confounders. In conclusion, longer sleep duration was independently associated with smaller LV mass, left atrial volume and RV volume. Evening chronotype was independently associated with smaller LV and RV and reduced RV function compared to morning chronotype. Sex interactions exist with cardiac remodeling most evident in males with long sleep duration and evening chronotype. Recommendations for sleep chronotype and duration may need to be individualized based on sex.
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Reply: Discourage LVNC or Revise the Criteria of LVNC?

Issue 6 Vol 16 Published on 2023-06-01 PMID 37286274 PMCID N/A
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DOI: https://doi.org/10.1016/j.jcmg.2023.03.023
Authors: Steffen E Petersen In X Bjarke Jensen In X Nay Aung In X Matthias G Friedrich In X Colin J McMahon In X Saidi A Mohiddin In X Ricardo H Pignatelli In X Fabrizio Ricci In X Robert H Anderson In X David A Bluemke In X
Abstract: No Abstract Available
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Conceptual Overview of Biological Age Estimation.

Open Access Issue 3 Vol 14 Published on 2023-06-01 PMID 37191413 PMCID PMC10187689
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DOI: https://doi.org/10.14336/ad.2022.1107
Authors: Ahmed Salih In X Thomas Nichols In X Liliana Szabo In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract: Chronological age is an imperfect measure of the aging process, which is affected by a wide range of genetic and environmental exposures. Biological age estimates may be derived using mathematical modelling with biomarkers set as predictors and chronological age as the output. The difference between biological and chronological age is denoted the "age gap" and considered a complementary indicator of aging. The utility of the "age gap" metric is assessed through examination of its associations with exposures of interest and the demonstration of additional information provided by this metric over chronological age alone. This paper reviews the key concepts of biological age estimation, the age gap metric, and approaches to assessment of model performance in this context. We further discuss specific challenges for the field, in particular the limited generalisability of effect sizes across studies owing to dependency of the age gap metric on pre-processing and model building methods. The discussion will be centred on brain age estimation, but the concepts are transferable to all biological age estimation.
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Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.

Open Access Issue 13 Vol 109 Published on 2023-06-01 PMID 37072241 PMCID PMC10314020
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Keywords: epidemiology, Magnetic Resonance Imaging
DOI: https://doi.org/10.1136/heartjnl-2022-321888
Authors: Zahra Raisi-Estabragh In X Jackie Cooper In X Celeste McCracken In X Emma J Crosbie In X Fiona M Walter In X Charlotte H Manisty In X John Robson In X Mamas A Mamas In X Nicholas C Harvey In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.
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Estimating Uncertainty in Neural Networks for Cardiac MRI Segmentation: A Benchmark Study.

Issue 6 Vol 70 Published on 2023-06-01 PMID 37015623 PMCID N/A
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DOI: https://doi.org/10.1109/tbme.2022.3232730
Authors: Matthew Ng In X Fumin Guo In X Labonny Biswas In X Steffen E Petersen In X Stefan K Piechnik In X Stefan Neubauer In X Graham Wright In X
Abstract:

Objective

Convolutional neural networks (CNNs) have demonstrated promise in automated cardiac magnetic resonance image segmentation. However, when using CNNs in a large real-world dataset, it is important to quantify segmentation uncertainty and identify segmentations which could be problematic. In this work, we performed a systematic study of Bayesian and non-Bayesian methods for estimating uncertainty in segmentation neural networks.

Methods

We evaluated Bayes by Backprop, Monte Carlo Dropout, Deep Ensembles, and Stochastic Segmentation Networks in terms of segmentation accuracy, probability calibration, uncertainty on out-of-distribution images, and segmentation quality control.

Results

We observed that Deep Ensembles outperformed the other methods except for images with heavy noise and blurring distortions. We showed that Bayes by Backprop is more robust to noise distortions while Stochastic Segmentation Networks are more resistant to blurring distortions. For segmentation quality control, we showed that segmentation uncertainty is correlated with segmentation accuracy for all the methods. With the incorporation of uncertainty estimates, we were able to reduce the percentage of poor segmentation to 5% by flagging 31-48% of the most uncertain segmentations for manual review, substantially lower than random review without using neural network uncertainty (reviewing 75-78% of all images).

Conclusion

This work provides a comprehensive evaluation of uncertainty estimation methods and showed that Deep Ensembles outperformed other methods in most cases.

Significance

Neural network uncertainty measures can help identify potentially inaccurate segmentations and alert users for manual review.
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The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.

Open Access Issue 7 Vol 24 Published on 2023-06-01 PMID 36660920 PMCID PMC10284050
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Keywords: Obesity, body mass index, Mediation, Cardiac Magnetic Resonance Imaging, Cardiovascular Remodelling, Waist-to-hip Ratio, Disease Mechanisms, Incident Cardiovascular Outcomes
DOI: https://doi.org/10.1093/ehjci/jeac270
Authors: Liliana Szabo In X Celeste McCracken In X Jackie Cooper In X Oliver J Rider In X Hajnalka Vago In X Bela Merkely In X Nicholas C Harvey In X Stefan Neubauer In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.
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Myocardial perfusion in excessively trabeculated hearts: Insights from imaging and histological studies.

Issue 6 Vol 81 Published on 2023-06-01 PMID 36481300 PMCID N/A
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Keywords: Blood flow, Cardiomyopathy, Noncompaction
DOI: https://doi.org/10.1016/j.jjcc.2022.11.013
Authors: Bjarke Jensen In X Steffen E Petersen In X Bram F Coolen In X
Abstract: In gestation, the coronary circulation develops initially in the compact layer and it expands only in fetal development to the trabeculations. Conflicting data have been published as to whether the trabecular layer is hypoperfused relative to the compact wall after birth. If so, this could explain the poor pump function in patients with left ventricular excessive trabeculation, or so-called noncompaction. Here, we review direct and indirect assessments of myocardial perfusion in normal and excessively trabeculated hearts by in vivo imaging by magnetic resonance imaging (MRI), positron emission tomography (PET)/single photon emission computed tomography (SPECT), and echocardiography in addition to histology, injections of labelled microspheres in animals, and electrocardiography. In MRI, PET/SPECT, and echocardiography, flow of blood or myocardial uptake of blood-borne tracer molecules are measured. The imaged trabecular layer comprises trabeculations and blood-filled intertrabecular spaces whereas the compact layer comprises tissue only, and spatio-temporal resolution likely affects measurements of myocardial perfusion differently in the two layers. Overall, studies measuring myocardial uptake of tracers (PET/SPECT) suggest trabecular hypoperfusion. Studies measuring the quantity of blood (echocardiography and MRI) suggest trabecular hyperperfusion. These conflicting results are reconciled if the low uptake from intertrabecular spaces in PET/SPECT and the high signal from intertrabecular spaces in MRI and echocardiography are considered opposite biases. Histology on human hearts reveal a similar capillary density of trabecular and compact myocardium. Injections of labelled microspheres in animals reveal a similar perfusion of trabecular and compact myocardium. In conclusion, trabecular and compact muscle are likely equally perfused in normal hearts and most cases of excessive trabeculation.
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Virtual cardiovascular magnetic resonance training proves feasible and effective: survey data from international participants of the CMR Academy Berlin, Germany.

Open Access Issue 1 Vol 1 Published on 2023-05-01 PMID 39044796 PMCID PMC11240162
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Keywords: Certification, Quality, Cardiology, Radiology, Cmr, Cardiovascular Magnetic Resonance Imaging, Online Education, Remote Education
DOI: https://doi.org/10.1093/ehjimp/qyad015
Authors: Djawid Hashemi In X Patrick Doeblin In X Karl Jakob Weiss In X Matthias Schneider-Reigbert In X Rebecca Elisabeth Beyer In X Corinna Else In X Alessandro Faragli In X Christian Stehning In X Philipp Stawowy In X Steffen E Petersen In X Chiara Bucciarelli-Ducci In X Allison G Hays In X Norbert Frey In X Holger Thiele In X Andreas Portmann In X Eckart Fleck In X Sebastian Kelle In X
Abstract:

Aims

This study aims to evaluate the success of the cardiovascular magnetic resonance (CMR) imaging Academy Berlin's transition from in-person to online CMR imaging training during the global pandemic 2020 and to gather recommendations for future courses.

Methods and results

We conducted an online survey targeting CMR course participants from both the pre-pandemic, in-person era and the pandemic, online era of the CMR Academy Berlin. The survey primarily used Likert-type questions to assess participants' experiences and preferences.A total of 61 out of 158 invited participants (38.61%) completed the survey, with 31 (50.82%) being in-person alumni and 30 (49.18%) being online alumni. Both in-person [83.87% (26/31)] and online [83.33% (25/30)] participants rated the course as either 'very good' or 'excellent', and both groups found the course either 'extremely helpful' or 'very helpful'. However, a higher percentage of in-person participants [96.77% (30/31)] felt comfortable asking questions compared to online participants [83.33% (25/30); P = 0.025]. The majority in both groups preferred a written exam [total: 75.41% (46/61); in-person alumni: 77.42% (24/31); online alumni 73.33% (22/30)]. In terms of course format preferences, in-person courses were preferred by both in-person alumni [38.71% (12/31)] and online alumni [60% (18/30)], almost as much as a hybrid format combining in-person and online elements [in-person alumni: 41.94% (13/31), online alumni: 30% (9/30)].

Conclusion

The transition from in-person to online CMR training at the CMR Academy Berlin was successful in maintaining overall satisfaction. However, there is room for improvement in terms of increased interaction, particularly for online participants. Future CMR- and potentially also cardiac computer tomography-courses should consider adopting a hybrid format to accommodate participants' preferences and enhance their learning experience, especially to gain level II competency, whereas level I virtual only might be sufficient.
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A somato-cognitive action network alternates with effector regions in motor cortex.

Open Access Issue 7960 Vol 617 Published on 2023-05-01 PMID 37076628 PMCID PMC10172144
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Keywords:
DOI: https://doi.org/10.1038/s41586-023-05964-2
Authors: Evan M Gordon In X Roselyne J Chauvin In X Andrew N Van In X Aishwarya Rajesh In X Ashley Nielsen In X Dillan J Newbold In X Charles J Lynch In X Nicole A Seider In X Samuel R Krimmel In X Kristen M Scheidter In X Julia Monk In X Ryland L Miller In X Athanasia Metoki In X David F Montez In X Annie Zheng In X Immanuel Elbau In X Thomas Madison In X Tomoyuki Nishino In X Michael J Myers In X Sydney Kaplan In X Carolina Badke D'Andrea In X Damion V Demeter In X Matthew Feigelis In X Julian S B Ramirez In X Ting Xu In X Deanna M Barch In X Christopher D Smyser In X Cynthia E Rogers In X Jan Zimmermann In X Kelly N Botteron In X John R Pruett In X Jon T Willie In X Peter Brunner In X Joshua S Shimony In X Benjamin P Kay In X Scott Marek In X Scott A Norris In X Caterina Gratton In X Chad M Sylvester In X Jonathan D Power In X Conor Liston In X Deanna J Greene In X Jarod L Roland In X Steven E Petersen In X Marcus E Raichle In X Timothy O Laumann In X Damien A Fair In X Nico U F Dosenbach In X
Abstract: Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.
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Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET.

Issue 5 Vol 16 Published on 2023-05-01 PMID 36881421 PMCID N/A
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Keywords: Positron emission tomography, coronary artery disease, myocardial perfusion imaging, Fractional Flow Reserve, Cardiac Magnetic Resonance, Chronic Coronary Syndrome
DOI: https://doi.org/10.1016/j.jcmg.2022.11.015
Authors: Laust Dupont Rasmussen In X Simon Winther In X Ashkan Eftekhari In X Salma Raghad Karim In X Jelmer Westra In X Christin Isaksen In X Lau Brix In X June Anita Ejlersen In X Theodore Murphy In X Xenios Milidonis In X Mette Nyegaard In X Mitchel Benovoy In X Jane Kirk Johansen In X Hanne Maare Søndergaard In X Osama Hammid In X Jesper Mortensen In X Lars Lyhne Knudsen In X Lars Christian Gormsen In X Evald Høj Christiansen In X Amedeo Chiribiri In X Steffen E Petersen In X Morten Böttcher In X
Abstract:

Background

Guidelines recommend verification of myocardial ischemia by selective second-line myocardial perfusion imaging (MPI) following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Head-to-head data on the diagnostic performance of different MPI modalities in this setting are sparse.

Objectives

The authors sought to compare, head-to-head, the diagnostic performance of selective MPI by 3.0-T cardiac magnetic resonance (CMR) and 82rubidium positron emission tomography (RbPET) in patients with suspected obstructive stenosis at coronary CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference.

Methods

Consecutive patients (n = 1,732, mean age: 59.1 ± 9.5 years, 57.2% men) referred for coronary CTA with symptoms suggestive of obstructive CAD were included. Patients with suspected stenosis were referred for both CMR and RbPET and subsequently ICA. Obstructive CAD was defined as FFR ≤0.80 or >90% diameter stenosis by visual assessment.

Results

In total, 445 patients had suspected stenosis on coronary CTA. Of these, 372 patients completed both CMR, RbPET and subsequent ICA with FFR. Hemodynamically obstructive CAD was identified in 164 of 372 (44.1%) patients. Sensitivities for CMR and RbPET were 59% (95% CI: 51%-67%) and 64% (95% CI: 56%-71%); P = 0.21, respectively, and specificities 84% (95% CI: 78%-89%) and 89% (95% CI: 84%-93%]); P = 0.08, respectively. Overall accuracy was higher for RbPET compared with CMR (73% vs 78%; P = 0.03).

Conclusions

In patients with suspected obstructive stenosis at coronary CTA, CMR, and RbPET show similar and moderate sensitivities but high specificities compared with ICA with FFR. This patient group represents a diagnostic challenge with frequent mismatch between advanced MPI tests and invasive measurements. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712).
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Prediction of incident cardiovascular events using machine learning and CMR radiomics.

Open Access Issue 5 Vol 33 Published on 2023-05-01 PMID 36512045 PMCID PMC10121487
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Keywords: Atrial fibrillation, Heart Failure, Preventive Medicine, Machine Learning, Radiomics
DOI: https://doi.org/10.1007/s00330-022-09323-z
Authors: Esmeralda Ruiz Pujadas In X Zahra Raisi-Estabragh In X Liliana Szabo In X Celeste McCracken In X Cristian Izquierdo Morcillo In X Víctor M Campello In X Carlos Martín-Isla In X Angelica M Atehortua In X Hajnalka Vago In X Bela Merkely In X Pal Maurovich-Horvat In X Nicholas C Harvey In X Stefan Neubauer In X Steffen E Petersen In X Karim Lekadir In X
Abstract:

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key points

• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.
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Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.

Issue 4 Vol 16 Published on 2023-04-01 PMID 37042240 PMCID N/A
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Keywords: Artificial intelligence, Diagnostic Imaging, Machine Learning, Cardiac Imaging Techniques
DOI: https://doi.org/10.1161/circimaging.122.014519
Authors: Ahmed Salih In X Ilaria Boscolo Galazzo In X Polyxeni Gkontra In X Aaron Mark Lee In X Karim Lekadir In X Zahra Raisi-Estabragh In X Steffen E Petersen In X
Abstract: Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.
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Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank.

Open Access Issue 4 Vol 16 Published on 2023-04-01 PMID 36648036 PMCID PMC10102720
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Keywords: Mortality, Cardiovascular disease, Cardiac Magnetic Resonance, Native T1 Mapping, Incident Events
DOI: https://doi.org/10.1016/j.jcmg.2022.06.011
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Evan Hann In X Dorina-Gabriela Condurache In X Nicholas C Harvey In X Patricia B Munroe In X Vanessa M Ferreira In X Stefan Neubauer In X Stefan K Piechnik In X Steffen E Petersen In X
Abstract:

Background

Cardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.

Objectives

The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.

Methods

Native T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.

Results

Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).

Conclusions

This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.
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Anatomy of the mitral valve relative to controversies concerning the so-called annular disjunction.

Issue 10 Vol 109 Published on 2023-04-01 PMID 36585240 PMCID N/A
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Keywords: Echocardiography, Mitral valve insufficiency, Diagnostic Imaging
DOI: https://doi.org/10.1136/heartjnl-2022-322043
Authors: Robert H Anderson In X Madalina Garbi In X Dasa Zugwitz In X Steffen E Petersen In X Robin Nijveldt In X
Abstract: It is now accepted that the mitral valve functions on the basis of a complex made up of the annulus, the leaflets, the tendinous cords and the papillary muscles. So as to work properly, these components must combine together in harmonious fashion. Despite the features of the arrangement of each component having been the focus of anatomical investigation for centuries, controversies still exist in their inter-relations and how best to describe them. To a large extent, the ongoing problems reflect the fact that, again for centuries, morphologists when describing the heart have ignored the rule that its components should be described as seen in the body during life. Failure to use attitudinally appropriate descriptions underscores a particular current issue, namely the influence of the so-called disjunction within the atrioventricular junction as a potential substrate for leaflet prolapse or malignant arrhythmias. With these difficulties in mind, we have reviewed how the components of the valvar complex can best be described when comparing direct images with those obtained using three-dimensional techniques now used for clinical imaging. We submit that these show that the skirt of leaflet tissue is best described as having aortic and mural components. When the hinge of the mural leaflet is assessed within the overall atrioventricular junction, the so-called disjunction is ubiquitous, but not always in the same place. We further suggest that its significance will best be determined when clinicians describe its presence using attitudinally appropriate terms.
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Autonomic Cardiovascular Control in Health and Disease.

Issue 2 Vol 13 Published on 2023-03-01 PMID 36994768 PMCID PMC10406398
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Keywords:
DOI: https://doi.org/10.1002/cphy.c210037
Authors: Shahid Karim In X Anwar Chahal In X Mohammed Y Khanji In X Steffen E Petersen In X Virend K Somers In X
Abstract: Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.
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Myocardial Tissue Characterization in Cardiac Magnetic Resonance Studies of Patients Recovering From COVID-19: A Meta-Analysis.

Open Access Issue 6 Vol 12 Published on 2023-03-01 PMID 36892052 PMCID PMC10111516
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Keywords: Cardiac Magnetic Resonance, Late Gadolinium Enhancement, Meta‐analysis, Extracellular Volume, Covid‐19, T1‐mapping, T2‐mapping
DOI: https://doi.org/10.1161/jaha.122.027801
Authors: Michael Jerosch-Herold In X Carsten Rickers In X Steffen E Petersen In X Otávio R Coelho-Filho In X
Abstract: Background Meta-analysis can identify biological factors that moderate cardiac magnetic resonance myocardial tissue markers such as native T1 (longitudinal magnetization relaxation time constant) and T2 (transverse magnetization relaxation time constant) in cohorts recovering from COVID-19 infection. Methods and Results Cardiac magnetic resonance studies of patients with COVID-19 using myocardial T1, T2 mapping, extracellular volume, and late gadolinium enhancement were identified by database searches. Pooled effect sizes and interstudy heterogeneity (I2) were estimated with random effects models. Moderators of interstudy heterogeneity were analyzed by meta-regression of the percent difference of native T1 and T2 between COVID-19 and control groups (%ΔT1 [percent difference of the study-level means of myocardial T1 in patients with COVID-19 and controls] and %ΔT2 [percent difference of the study-level means of myocardial T2 in patients with COVID-19 and controls]), extracellular volume, and the proportion of late gadolinium enhancement. Interstudy heterogeneities of %ΔT1 (I2=76%) and %ΔT2 (I2=88%) were significantly lower than for native T1 and T2, respectively, independent of field strength, with pooled effect sizes of %ΔT1=1.24% (95% CI, 0.54%-1.9%) and %ΔT2=3.77% (95% CI, 1.79%-5.79%). %ΔT1 was lower for studies in children (median age: 12.7 years) and athletes (median age: 21 years), compared with older adults (median age: 48 years). Duration of recovery from COVID-19, cardiac troponins, C-reactive protein, and age were significant moderators for %ΔT1 and/or %ΔT2. Extracellular volume, adjusted by age, was moderated by recovery duration. Age, diabetes, and hypertension were significant moderators of the proportion of late gadolinium enhancement in adults. Conclusions T1 and T2 are dynamic markers of cardiac involvement in COVID-19 that reflect the regression of cardiomyocyte injury and myocardial inflammation during recovery. Late gadolinium enhancement and to a lesser extent extracellular volume, are more static biomarkers moderated by preexisting risk factors linked to adverse myocardial tissue remodeling.
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Excessive Trabeculation of the Left Ventricle: JACC: Cardiovascular Imaging Expert Panel Paper.

Open Access Issue 3 Vol 16 Published on 2023-03-01 PMID 36764891 PMCID PMC9988693
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Keywords: Etiology, Diagnosis, Prognosis, Clinical Management, Left Ventricular Noncompaction, Cardiovascular Imaging
DOI: https://doi.org/10.1016/j.jcmg.2022.12.026
Authors: Steffen E Petersen In X Bjarke Jensen In X Nay Aung In X Matthias G Friedrich In X Colin J McMahon In X Saidi A Mohiddin In X Ricardo H Pignatelli In X Fabrizio Ricci In X Robert H Anderson In X David A Bluemke In X
Abstract: Excessive trabeculation, often referred to as "noncompacted" myocardium, has been described at all ages, from the fetus to the adult. Current evidence for myocardial development, however, does not support the formation of compact myocardium from noncompacted myocardium, nor the arrest of this process to result in so-called noncompaction. Excessive trabeculation is frequently observed by imaging studies in healthy individuals, as well as in association with pregnancy, athletic activity, and with cardiac diseases of inherited, acquired, developmental, or congenital origins. Adults with incidentally noted excessive trabeculation frequently require no further follow-up based on trabecular pattern alone. Patients with cardiomyopathy and excessive trabeculation are managed by cardiovascular symptoms rather than the trabecular pattern. To date, the prognostic role of excessive trabeculation in adults has not been shown to be independent of other myocardial disease. In neonates and children with excessive trabeculation and normal or abnormal function, clinical caution seems warranted because of the reported association with genetic and neuromuscular disorders. This report summarizes the evidence concerning the etiology, pathophysiology, and clinical relevance of excessive trabeculation. Gaps in current knowledge of the clinical relevance of excessive trabeculation are indicated, with priorities suggested for future research and improved diagnosis in adults and children.
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Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.

Open Access Issue 7 Vol 109 Published on 2023-03-01 PMID 36384749 PMCID PMC10086465
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Keywords: epidemiology, Magnetic Resonance Imaging, risk factors
DOI: https://doi.org/10.1136/heartjnl-2022-321733
Authors: Zahra Raisi-Estabragh In X Jackie Cooper In X Mae S Bethell In X Celeste McCracken In X Adam J Lewandowski In X Paul Leeson In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.
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Maturation of large-scale brain systems over the first month of life.

Issue 6 Vol 33 Published on 2023-03-01 PMID 35750056 PMCID PMC10016041
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Keywords: Development, Infant, fMRI, Machine Learning, Functional Connectivity
DOI: https://doi.org/10.1093/cercor/bhac242
Authors: Ashley N Nielsen In X Sydney Kaplan In X Dominique Meyer In X Dimitrios Alexopoulos In X Jeanette K Kenley In X Tara A Smyser In X Lauren S Wakschlag In X Elizabeth S Norton In X Nandini Raghuraman In X Barbara B Warner In X Joshua S Shimony In X Joan L Luby In X Jeffery J Neil In X Steven E Petersen In X Deanna M Barch In X Cynthia E Rogers In X Chad M Sylvester In X Christopher D Smyser In X
Abstract: The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child's earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain "growth curve" that could be used to identify atypical brain maturation in infancy.
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Genome-Wide Analysis of Left Ventricular Maximum Wall Thickness in the UK Biobank Cohort Reveals a Shared Genetic Background With Hypertrophic Cardiomyopathy.

Open Access Issue 1 Vol 16 Published on 2023-02-01 PMID 36598836 PMCID PMC9946169
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Keywords: hypertrophic cardiomyopathy, loci, Risk Score, Cardiovascular Magnetic Resonance, Odds Ratio
DOI: https://doi.org/10.1161/circgen.122.003716
Authors: Nay Aung In X Luis R Lopes In X Stefan van Duijvenboden In X Andrew R Harper In X Anuj Goel In X Christopher Grace In X Carolyn Y Ho In X William S Weintraub In X Christopher M Kramer In X Stefan Neubauer In X Hugh C Watkins In X Steffen E Petersen In X Patricia B Munroe In X
Abstract:

Background

Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT.

Methods

We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study.

Results

Twenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=0.53) and substantial loci overlap (19/21).

Conclusions

Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.
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EACVI SIMULATOR-online study: evaluation of transoesophageal echocardiography knowledge and skills of young cardiologists.

Issue 3 Vol 24 Published on 2023-02-01 PMID 36151868 PMCID N/A
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Keywords: Simulation, Knowledge, Education, Skills, Transesophageal Echocardiography (Toe)
DOI: https://doi.org/10.1093/ehjci/jeac195
Authors: Théo Pezel In X Augustin Coisne In X Błażej Michalski In X Hatem Soliman In X Nina Ajmone In X Robin Nijveldt In X Ivan Stankovic In X Erwan Donal In X Joost van der Maaten In X Constantinos Papadopoulos In X Thor Edvardsen In X Denisa Muraru In X Steffen E Petersen In X Bernard Cosyns In X Magnus Bäck In X Philippe B Bertrand In X Kristina H Haugaa In X Niall Keenan In X Erwan Donal In X Bernard Cosyns In X
Abstract:

Aims

To assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists.

Methods and results

A European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9-12 December 2021 and 10-13 April 2022). All young cardiologists eligible to participate (<40 years) across the world were invited to participate. After a short survey, each participant completed two tests: a theoretical test to assess TOE knowledge and a practical test using an online TOE simulator to investigate TOE skills. Among 716 young cardiologists from 81 countries, the mean theoretical test score was 56.8 ± 20.9 points, and the mean practical test score was 47.4 ± 7.2 points (/100 points max each), including 18.4 ± 8.7 points for the acquisition test score and 29.0 ± 6.7 points for the anatomy test score (/50 points max each). Acquisition test scores were higher for four-chamber (2.3 ± 1.5 points), two-chamber (2.2 ± 1.4 points) and three-chamber views (2.3 ± 1.4 points) than for other views (all P < 0.001). Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and EACVI certification for TOE were independently associated with a higher global score (all P < 0.001).

Conclusion

Online evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score.
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Network-specific selectivity of functional connections in the neonatal brain.

Issue 5 Vol 33 Published on 2023-02-01 PMID 35595540 PMCID PMC9977389
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Keywords: Infant, fMRI, Neonate, Networks, Functional Connectivity
DOI: https://doi.org/10.1093/cercor/bhac202
Authors: Chad M Sylvester In X Sydney Kaplan In X Michael J Myers In X Evan M Gordon In X Rebecca F Schwarzlose In X Dimitrios Alexopoulos In X Ashley N Nielsen In X Jeanette K Kenley In X Dominique Meyer In X Qiongru Yu In X Alice M Graham In X Damien A Fair In X Barbara B Warner In X Deanna M Barch In X Cynthia E Rogers In X Joan L Luby In X Steven E Petersen In X Christopher D Smyser In X
Abstract: The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.
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Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.

Open Access Issue N/A Vol 10 Published on 2023-01-01 PMID 37781298 PMCID PMC10541220
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Keywords: Machine Learning (Ml), Radiomics, Cmr (Cardiovascular Magnetic Resonance), Dan-nicad, Stress Perfusion Cardiac Mri
DOI: https://doi.org/10.3389/fcvm.2023.1141026
Authors: Zahra Raisi-Estabragh In X Carlos Martin-Isla In X Louise Nissen In X Liliana Szabo In X Victor M Campello In X Sergio Escalera In X Simon Winther In X Morten Bøttcher In X Karim Lekadir In X Steffen E Petersen In X
Abstract:

Objectives

To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.

Methods

We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (n = 14) and texture (n = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.

Results

Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.

Conclusion

In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.
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Prognostic role of renal replacement therapy among hospitalized patients with heart failure in the Brazilian national public health system.

Open Access Issue N/A Vol 10 Published on 2023-01-01 PMID 37680567 PMCID PMC10482263
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Keywords: Mortality, Heart Failure, Hospitalization, Chronic Kidney Disease, Acute Kidney Injury, Renal Replacement Therapy, Cardio-renal Syndrome
DOI: https://doi.org/10.3389/fcvm.2023.1226481
Authors: Andréa Coy-Canguçu In X Lígia M Antunes-Correa In X Marilda Mazzali In X Paula Abrão In X Fernanda Ronco In X Cinthia Montenegro Teixeira In X Karynna Pimentel Viana In X Guilherme Cordeiro In X Mauricio Longato In X Otávio Rizzi Coelho In X José Roberto Matos-Souza In X Wilson Nadruz In X Andrei C Sposito In X Steffen E Petersen In X Michael Jerosch-Herold In X Otávio Rizzi Coelho-Filho In X
Abstract:

Introduction

Data on patients hospitalized with acute heart failure in Brazil scarce.

Methods

We performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome.

Results

In total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p < 0.001]) was associated with a 56% increase in the risk of death in the univariate regression model (HR 1.56, 95% CI 1.52 -1.59), a more than threefold increase of the duration of hospitalization, and a 45% or greater increase of cost per day. All forms of renal replacement therapy remained independently associated with in-hospital mortality in multivariable analysis (intermittent hemodialysis: HR 1.64, 95% CI 1.60 -1.69; continuous hemodialysis: HR 1.52, 95% CI 1.42 -1.63; peritoneal dialysis: HR 1.47, 95% CI 1.20 -1.88).

Discussion

The in-hospital mortality rate of 11.7% observed among patients with acute heart failure admitted to Brazilian public hospitals was alarmingly high, exceeding that of patients admitted to North American and European institutions. This is the first report to quantify the rate of renal replacement therapy in patients hospitalized with acute heart failure in Brazil.
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Editorial: Current and future role of artificial intelligence in cardiac imaging, volume II.

Open Access Issue N/A Vol 10 Published on 2023-01-01 PMID 37363092 PMCID PMC10285516
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Keywords: Artificial intelligence, Big Data, Cardiac Image Analysis, Ai Adoption And Translation, Cardiac Imaging Modalities, Cardiovascular Personalized Medicine
DOI: https://doi.org/10.3389/fcvm.2023.1220836
Authors: Tim Leiner In X Karim Lekadir In X Steffen E Petersen In X Alistair A Young In X
Abstract: No Abstract Available
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Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.

Open Access Issue N/A Vol 10 Published on 2023-01-01 PMID 37180793 PMCID PMC10167048
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Keywords: Diabetes, Sex differences, epidemiology, Heart Failure, Morgam
DOI: https://doi.org/10.3389/fcvm.2023.1136764
Authors: Sucharitha Chadalavada In X Jaakko Reinikainen In X Jonas Andersson In X Augusto Di Castelnuovo In X Licia Iacoviello In X Pekka Jousilahti In X Line Lund Kårhus In X Allan Linneberg In X Stefan Söderberg In X Hugh Tunstall-Pedoe In X Karim Lekadir In X Nay Aung In X Magnus T Jensen In X Kari Kuulasmaa In X Teemu J Niiranen In X Steffen E Petersen In X
Abstract:

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.
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A Prospective Evaluation of Infant Cerebellar-Cerebral Functional Connectivity in Relation to Behavioral Development in Autism Spectrum Disorder.

Open Access Issue 1 Vol 3 Published on 2023-01-01 PMID 36712571 PMCID PMC9874081
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Keywords: Development, Cerebellum, Infancy, Autism, Functional Connectivity, Error-based Learning
DOI: https://doi.org/10.1016/j.bpsgos.2021.12.004
Authors: Zoë W Hawks In X Alexandre Todorov In X Natasha Marrus In X Tomoyuki Nishino In X Muhamed Talovic In X Mary Beth Nebel In X Jessica B Girault In X Savannah Davis In X Scott Marek In X Benjamin A Seitzman In X Adam T Eggebrecht In X Jed Elison In X Stephen Dager In X Matthew W Mosconi In X Lawrence Tychsen In X Abraham Z Snyder In X Kelly Botteron In X Annette Estes In X Alan Evans In X Guido Gerig In X Heather C Hazlett In X Robert C McKinstry In X Juhi Pandey In X Robert T Schultz In X Martin Styner In X Jason J Wolff In X Lonnie Zwaigenbaum In X Lori Markson In X Steven E Petersen In X John N Constantino In X Desirée A White In X Joseph Piven In X John R Pruett In X
Abstract:

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection.

Methods

Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning-based predictive tests examined cerebellar-frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar-default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections.

Results

Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections.

Conclusions

We failed to identify cerebellar functional connectivity-based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.
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Response to: Correspondence on 'Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank' by Jolobe.

Issue N/A Vol N/A Published on 2023-01-01 PMID 36593100 PMCID N/A
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Keywords: epidemiology, acute coronary syndrome, Covid-19
DOI: https://doi.org/10.1136/heartjnl-2022-322124
Authors: Zahra Raisi-Estabragh In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract: No Abstract Available
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Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.

Issue 2 Vol 44 Published on 2023-01-01 PMID 36452988 PMCID N/A
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Keywords: Imaging, coronary artery disease, Chronic Coronary Syndromes
DOI: https://doi.org/10.1093/eurheartj/ehac640
Authors: Danilo Neglia In X Riccardo Liga In X Alessia Gimelli In X Tomaž Podlesnikar In X Marta Cvijić In X Gianluca Pontone In X Marcelo Haertel Miglioranza In X Andrea Igoren Guaricci In X Sara Seitun In X Alberto Clemente In X Alexey Sumin In X João Vitola In X Antti Saraste In X Christian Paunonen In X Ching-Hui Sia In X Filipp Paleev In X Leyla Elif Sade In X Jose Luis Zamorano In X Natallia Maroz-Vadalazhskaya In X Constantinos Anagnostopoulos In X Filipe Macedo In X Juhani Knuuti In X Thor Edvardsen In X Bernard Cosyns In X Steffen E Petersen In X Julien Magne In X Cecile Laroche In X Clara Berlè In X Bogdan A Popescu In X Victoria Delgado In X In X
Abstract:

Background

The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS).

Methods

Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD).

Results

The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization.

Conclusions

In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior.
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DragNet: Learning-based deformable registration for realistic cardiac MR sequence generation from a single frame.

Issue N/A Vol 83 Published on 2023-01-01 PMID 36403308 PMCID N/A
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Keywords: Uncertainty Estimation, Uk Biobank, Deep Learning, Deformable Temporal Image Registration, Sequential Image Data Generation, Variational Recurrent Neural Networks
DOI: https://doi.org/10.1016/j.media.2022.102678
Authors: Arezoo Zakeri In X Alireza Hokmabadi In X Ning Bi In X Isuru Wijesinghe In X Michael G Nix In X Steffen E Petersen In X Alejandro F Frangi In X Zeike A Taylor In X Ali Gooya In X
Abstract: Deformable image registration (DIR) can be used to track cardiac motion. Conventional DIR algorithms aim to establish a dense and non-linear correspondence between independent pairs of images. They are, nevertheless, computationally intensive and do not consider temporal dependencies to regulate the estimated motion in a cardiac cycle. In this paper, leveraging deep learning methods, we formulate a novel hierarchical probabilistic model, termed DragNet, for fast and reliable spatio-temporal registration in cine cardiac magnetic resonance (CMR) images and for generating synthetic heart motion sequences. DragNet is a variational inference framework, which takes an image from the sequence in combination with the hidden states of a recurrent neural network (RNN) as inputs to an inference network per time step. As part of this framework, we condition the prior probability of the latent variables on the hidden states of the RNN utilised to capture temporal dependencies. We further condition the posterior of the motion field on a latent variable from hierarchy and features from the moving image. Subsequently, the RNN updates the hidden state variables based on the feature maps of the fixed image and the latent variables. Different from traditional methods, DragNet performs registration on unseen sequences in a forward pass, which significantly expedites the registration process. Besides, DragNet enables generating a large number of realistic synthetic image sequences given only one frame, where the corresponding deformations are also retrieved. The probabilistic framework allows for computing spatio-temporal uncertainties in the estimated motion fields. Our results show that DragNet performance is comparable with state-of-the-art methods in terms of registration accuracy, with the advantage of offering analytical pixel-wise motion uncertainty estimation across a cardiac cycle and being a motion generator. We will make our code publicly available.
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Quantification of Epicardial Adipose Tissue Volume and Attenuation for Cardiac CT Scans Using Deep Learning in a Single Multi-Task Framework.

Open Access Issue 12 Vol 23 Published on 2022-12-01 PMID 39076659 PMCID PMC11270472
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Keywords: Density, Volume, CT, Attenuation, Epicardial Adipose Tissue, Eat, Deep Learning
DOI: https://doi.org/10.31083/j.rcm2312412
Authors: Musa Abdulkareem In X Mark S Brahier In X Fengwei Zou In X Elisa Rauseo In X Ijeoma Uchegbu In X Alexandra Taylor In X Athanasios Thomaides In X Peter J Bergquist In X Monvadi B Srichai In X Aaron M Lee In X Jose D Vargas In X Steffen E Petersen In X
Abstract:

Background

Recent studies have shown that epicardial adipose tissue (EAT) is an independent atrial fibrillation (AF) prognostic marker and has influence on the myocardial function. In computed tomography (CT), EAT volume (EATv) and density (EATd) are parameters that are often used to quantify EAT. While increased EATv has been found to correlate with the prevalence and the recurrence of AF after ablation therapy, higher EATd correlates with inflammation due to arrest of lipid maturation and with high risk of plaque presence and plaque progression. Automation of the quantification task diminishes the variability in readings introduced by different observers in manual quantification and results in high reproducibility of studies and less time-consuming analysis. Our objective is to develop a fully automated quantification of EATv and EATd using a deep learning (DL) framework.

Methods

We proposed a framework that consists of image classification and segmentation DL models and performs the task of selecting images with EAT from all the CT images acquired for a patient, and the task of segmenting the EAT from the output images of the preceding task. EATv and EATd are estimated using the segmentation masks to define the region of interest. For our experiments, a 300-patient dataset was divided into two subsets, each consisting of 150 patients: Dataset 1 (41,979 CT slices) for training the DL models, and Dataset 2 (36,428 CT slices) for evaluating the quantification of EATv and EATd.

Results

The classification model achieved accuracies of 98% for precision, recall and F1 scores, and the segmentation model achieved accuracies in terms of mean ( ± std.) and median dice similarity coefficient scores of 0.844 ( ± 0.19) and 0.84, respectively. Using the evaluation set (Dataset 2), our approach resulted in a Pearson correlation coefficient of 0.971 ( R2 = 0.943) between the label and predicted EATv, and the correlation coefficient of 0.972 ( R2 = 0.945) between the label and predicted EATd.

Conclusions

We proposed a framework that provides a fast and robust strategy for accurate EAT segmentation, and volume (EATv) and attenuation (EATd) quantification tasks. The framework will be useful to clinicians and other practitioners for carrying out reproducible EAT quantification at patient level or for large cohorts and high-throughput projects.
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Making Less of a Mess of the Trabecular Mesh.

Issue 6 Vol 4 Published on 2022-12-01 PMID 36601457 PMCID PMC9806725
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Keywords:
DOI: https://doi.org/10.1148/ryct.220227
Authors: Bjarke Jensen In X Steffen E Petersen In X
Abstract: No Abstract Available
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Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.

Open Access Issue 1 Vol 13 Published on 2022-12-01 PMID 36543768 PMCID PMC9772225
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Keywords:
DOI: https://doi.org/10.1038/s41467-022-35321-2
Authors: Celeste McCracken In X Zahra Raisi-Estabragh In X Michele Veldsman In X Betty Raman In X Andrea Dennis In X Masud Husain In X Thomas E Nichols In X Steffen E Petersen In X Stefan Neubauer In X
Abstract: Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.
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Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.

Open Access Issue 2 Vol 109 Published on 2022-12-01 PMID 36280346 PMCID PMC9811071
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Keywords: epidemiology, Covid-19
DOI: https://doi.org/10.1136/heartjnl-2022-321492
Authors: Zahra Raisi-Estabragh In X Jackie Cooper In X Ahmed Salih In X Betty Raman In X Aaron Mark Lee In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Objective

To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.
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'The Digital Cardiologist': How Technology Is Changing the Paradigm of Cardiology Training.

Issue 12 Vol 47 Published on 2022-12-01 PMID 36100095 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.cpcardiol.2022.101394
Authors: Sebastian Vandermolen In X Fabrizio Ricci In X C Anwar A Chahal In X Claudio Capelli In X Khalid Barakat In X Artur Fedorowski In X Mark Westwood In X Riyaz S Patel In X Steffen E Petersen In X Sabina Gallina In X Francesca Pugliese In X Mohammed Y Khanji In X
Abstract: In the same way that the practice of cardiology has evolved over the years, so too has the way cardiology fellows in training (FITs) are trained. Propelled by recent advances in technology-catalyzed by COVID-19-and the requirement to adapt age-old methods of both teaching and health care delivery, many aspects, or 'domains', of learning have changed. These include the environments in which FITs work (outpatient clinics, 'on-call' inpatient service) and procedures in which they need clinical competency. Further advances in virtual reality are also changing the way FITs learn and interact. The proliferation of technology into the cardiology curriculum has led to some describing the need for FITs to develop into 'digital cardiologists', namely those who comfortably use digital tools to aid clinical practice, teaching, and training whilst, at the same time, retain the ability for human analysis and nuanced assessment so important to patient-centred training and clinical care.
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Artificial Intelligence and Cardiovascular Magnetic Resonance Imaging in Myocardial Infarction Patients.

Issue 12 Vol 47 Published on 2022-12-01 PMID 35870544 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.cpcardiol.2022.101330
Authors: Jun Hua Chong In X Musa Abdulkareem In X Steffen E Petersen In X Mohammed Y Khanji In X
Abstract: Cardiovascular magnetic resonance (CMR) is an important cardiac imaging tool for assessing the prognostic extent of myocardial injury after myocardial infarction (MI). Within the context of clinical trials, CMR is also useful for assessing the efficacy of potential cardioprotective therapies in reducing MI size and preventing adverse left ventricular (LV) remodelling in reperfused MI. However, manual contouring and analysis can be time-consuming with interobserver and intra-observer variability, which can in turn lead to reduction in accuracy and precision of analysis. There is thus a need to automate CMR scan analysis in MI patients to save time, increase accuracy, increase reproducibility and increase precision. In this regard, automated imaging analysis techniques based on artificial intelligence (AI) that are developed with machine learning (ML), and more specifically deep learning (DL) strategies, can enable efficient, robust, accurate and clinician-friendly tools to be built so as to try and improve both clinician productivity and quality of patient care. In this review, we discuss basic concepts of ML in CMR, important prognostic CMR imaging biomarkers in MI and the utility of current ML applications in their analysis as assessed in research studies. We highlight potential barriers to the mainstream implementation of these automated strategies and discuss related governance and quality control issues. Lastly, we discuss the future role of ML applications in clinical trials and the need for global collaboration in growing this field.
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Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.

Open Access Issue 1 Vol 9 Published on 2022-12-01 PMID 35435219 PMCID PMC9745666
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Keywords: Cancer, Cardiovascular disease, epidemiology, Cardiovascular Mortality, Mortality Trends, Cardio-oncology
DOI: https://doi.org/10.1093/ehjqcco/qcac016
Authors: Zahra Raisi-Estabragh In X Ofer Kobo In X Phillip Freeman In X Steffen E Petersen In X Louis Kolman In X Robert J H Miller In X Ariel Roguin In X Harriette G C Van Spall In X Jacqueline Vuong In X Eric H Yang In X Mamas A Mamas In X
Abstract:

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.
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The Future of Cardiac Magnetic Resonance Clinical Trials.

Issue 12 Vol 15 Published on 2022-12-01 PMID 34922874 PMCID N/A
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Keywords: Clinical Trials, Cardiac Magnetic Resonance
DOI: https://doi.org/10.1016/j.jcmg.2021.07.029
Authors: Mark G Rabbat In X Raymond Y Kwong In X John F Heitner In X Alistair A Young In X Sujata M Shanbhag In X Steffen E Petersen In X Joseph B Selvanayagam In X Colin Berry In X Eike Nagel In X Bobak Heydari In X Alicia M Maceira In X Chetan Shenoy In X Christopher Dyke In X Kenneth C Bilchick In X In X
Abstract: Over the past 2 decades, cardiac magnetic resonance (CMR) has become an essential component of cardiovascular clinical care and contributed to imaging-guided diagnosis and management of coronary artery disease, cardiomyopathy, congenital heart disease, cardio-oncology, valvular, and vascular disease, amongst others. The widespread availability, safety, and capability of CMR to provide corresponding anatomical, physiological, and functional data in 1 imaging session can improve the design and conduct of clinical trials through both a reduction of sample size and provision of important mechanistic data that may augment clinical trial findings. Moreover, prospective imaging-guided strategies using CMR can enhance safety, efficacy, and cost-effectiveness of cardiovascular pathways in clinical practice around the world. As the future of large-scale clinical trial design evolves to integrate personalized medicine, cost-effectiveness, and mechanistic insights of novel therapies, the integration of CMR will continue to play a critical role. In this document, the attributes, limitations, and challenges of CMR's integration into the future design and conduct of clinical trials will also be covered, and recommendations for trialists will be explored. Several prominent examples of clinical trials that test the efficacy of CMR-imaging guided pathways will also be discussed.
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Atrial fibrillation prediction by combining ECG markers and CMR radiomics.

Open Access Issue 1 Vol 12 Published on 2022-11-01 PMID 36344532 PMCID PMC9640662
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Keywords:
DOI: https://doi.org/10.1038/s41598-022-21663-w
Authors: Esmeralda Ruiz Pujadas In X Zahra Raisi-Estabragh In X Liliana Szabo In X Cristian Izquierdo Morcillo In X Víctor M Campello In X Carlos Martin-Isla In X Hajnalka Vago In X Bela Merkely In X Nicholas C Harvey In X Steffen E Petersen In X Karim Lekadir In X
Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p < 0.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p < 0.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.
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The year 2021 in the European Heart Journal-Cardiovascular Imaging: Part I.

Issue 12 Vol 23 Published on 2022-11-01 PMID 36308337 PMCID N/A
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Keywords: Nuclear, Echocardiography, Multimodality Imaging, Cardiac Magnetic Resonance (Cmr), Computer Tomography (Ct)
DOI: https://doi.org/10.1093/ehjci/jeac210
Authors: Thor Edvardsen In X Erwan Donal In X Denisa Muraru In X Alessia Gimelli In X Ricardo Fontes-Carvalho In X Gerald Maurer In X Steffen E Petersen In X Bernard Cosyns In X
Abstract: The European Heart Journal-Cardiovascular Imaging was introduced in 2012 and has during these 10 years become one of the leading multimodality cardiovascular imaging journals. The journal is currently ranked as Number 19 among all cardiovascular journals. It has an impressive impact factor of 9.130 and our journal is well established as one of the top cardiovascular journals. The most important studies published in our Journal in 2021 will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
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Mitral Annular Disjunction Assessed Using CMR Imaging: Insights From the UK Biobank Population Study.

Open Access Issue 11 Vol 15 Published on 2022-11-01 PMID 36280553 PMCID PMC9640354
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Keywords: Cardiac Magnetic Resonance, Mitral Valve Prolapse, Mitral Annular Disjunction
DOI: https://doi.org/10.1016/j.jcmg.2022.07.015
Authors: Dasa Zugwitz In X Kenneth Fung In X Nay Aung In X Elisa Rauseo In X Celeste McCracken In X Jackie Cooper In X Saloua El Messaoudi In X Robert H Anderson In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Robin Nijveldt In X
Abstract:

Background

Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known.

Objectives

The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort.

Methods

The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall.

Results

From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01).

Conclusions

This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding.
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Benefits of Machine Learning to Predict Survival Using Stress Perfusion CMR and Basic Clinical Information.

Issue 11 Vol 15 Published on 2022-11-01 PMID 35987738 PMCID N/A
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Keywords: Machine Learning, Cardiovascular Magnetic Resonance, Vasodilator Stress Perfusion
DOI: https://doi.org/10.1016/j.jcmg.2022.06.017
Authors: Steffen E Petersen In X Nay Aung In X
Abstract: No Abstract Available
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Differential Patterns and Outcomes of 20.6 Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.

Open Access Issue 19 Vol 11 Published on 2022-10-01 PMID 36073628 PMCID PMC9673731
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Keywords: Men, Essential hypertension, Atrial fibrillation, Stroke, Women, Sex characteristics, United States
DOI: https://doi.org/10.1161/jaha.122.026432
Authors: Zahra Raisi-Estabragh In X Ofer Kobo In X Ayman Elbadawi In X Poonam Velagapudi In X Garima Sharma In X Renee P Bullock-Palmer In X Steffen E Petersen In X Laxmi S Mehta In X Waqas Ullah In X Ariel Roguin In X Louise Y Sun In X Mamas A Mamas In X
Abstract: Background We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.
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2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.

Issue 39 Vol 43 Published on 2022-10-01 PMID 36017553 PMCID N/A
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Keywords: Biomarkers, Guidelines, Non-cardiac Surgery, Anti-thrombotic Therapy, Pre-operative Cardiac Risk Assessment, Pre-operative Coronary Artery Revascularization, Peri-operative Cardiac Management, Post-operative Cardiac Surveillance, Pre-operative Cardiac Testing, Peri-operative Treatment Of Arrhythmias, Pre-operative Treatment Of Valvular Disease, Peri-operative Beta-blockers, Peri-operative Myocardial Injury/infarction
DOI: https://doi.org/10.1093/eurheartj/ehac270
Authors: Sigrun Halvorsen In X Julinda Mehilli In X Salvatore Cassese In X Trygve S Hall In X Magdy Abdelhamid In X Emanuele Barbato In X Stefan De Hert In X Ingrid de Laval In X Tobias Geisler In X Lynne Hinterbuchner In X Borja Ibanez In X Radosław Lenarczyk In X Ulrich R Mansmann In X Paul McGreavy In X Christian Mueller In X Claudio Muneretto In X Alexander Niessner In X Tatjana S Potpara In X Arsen Ristić In X L Elif Sade In X Henrik Schirmer In X Stefanie Schüpke In X Henrik Sillesen In X Helge Skulstad In X Lucia Torracca In X Oktay Tutarel In X Peter Van Der Meer In X Wojtek Wojakowski In X Kai Zacharowski In X In X
Abstract: No Abstract Available
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2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.

Issue 38 Vol 43 Published on 2022-10-01 PMID 36017548 PMCID N/A
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Keywords: Congenital heart disease, Lung disease, Pulmonary hypertension, Lung transplantation, Guidelines, Pulmonary Arterial Hypertension, Pulmonary Endarterectomy, Endothelin Receptor Antagonists, Connective Tissue Disease, Phosphodiesterase Type 5 Inhibitors, Chronic Thrombo-embolic Pulmonary Hypertension, Left Heart Disease, Prostacyclin Analogues, Balloon Pulmonary Angioplasty, Prostacyclin Receptor Agonists, Soluble Guanylate Cyclase Stimulators
DOI: https://doi.org/10.1093/eurheartj/ehac237
Authors: Marc Humbert In X Gabor Kovacs In X Marius M Hoeper In X Roberto Badagliacca In X Rolf M F Berger In X Margarita Brida In X Jørn Carlsen In X Andrew J S Coats In X Pilar Escribano-Subias In X Pisana Ferrari In X Diogenes S Ferreira In X Hossein Ardeschir Ghofrani In X George Giannakoulas In X David G Kiely In X Eckhard Mayer In X Gergely Meszaros In X Blin Nagavci In X Karen M Olsson In X Joanna Pepke-Zaba In X Jennifer K Quint In X Göran Rådegran In X Gerald Simonneau In X Olivier Sitbon In X Thomy Tonia In X Mark Toshner In X Jean Luc Vachiery In X Anton Vonk Noordegraaf In X Marion Delcroix In X Stephan Rosenkranz In X In X
Abstract: No Abstract Available
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Impact of cancer diagnosis on distribution and trends of cardiovascular hospitalizations in the USA between 2004 and 2017.

Issue 7 Vol 8 Published on 2022-10-01 PMID 35913736 PMCID PMC9603542
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Keywords: Prognosis, trends, Cardio- Oncology
DOI: https://doi.org/10.1093/ehjqcco/qcac045
Authors: Ofer Kobo In X Zahra Raisi-Estabragh In X Sofie Gevaert In X Jamal S Rana In X Harriette G C Van Spall In X Ariel Roguin In X Steffen E Petersen In X Bonnie Ky In X Mamas A Mamas In X
Abstract:

Background and aims

There is limited data on temporal trends of cardiovascular hospitalizations and outcomes amongst cancer patients. We describe the distribution, trends of admissions, and in-hospital mortality associated with key cardiovascular diseases among cancer patients in the USA between 2004 and 2017.

Methods

Using the Nationwide Inpatient Sample we, identified admissions with five cardiovascular diseases of interest: acute myocardial infarction (AMI), pulmonary embolism (PE), ischaemic stroke, heart failure, atrial fibrillation (AF) or atrial flutter, and intracranial haemorrhage. Patients were stratified by cancer status and type. We estimated crude annual rates of hospitalizations and annual in-hospital all-cause mortality rates.

Results

From >42.5 million hospitalizations with a primary cardiovascular diagnosis, 1.9 million (4.5%) had a concurrent record of cancer. Between 2004 and 2017, cardiovascular admission rates increased by 23.2% in patients with cancer, whilst decreasing by 10.9% in patients without cancer. The admission rate increased among cancer patients across all admission causes and cancer types except prostate cancer. Patients with haematological (9.7-13.5), lung (7.4-8.9), and GI cancer (4.6-6.3) had the highest crude rates of cardiovascular hospitalizations per 100 000 US population. Heart failure was the most common reason for cardiovascular admission in patients across all cancer types, except GI cancer (crude admission rates of 13.6-16.6 per 100 000 US population for patients with cancer).

Conclusions

In contrast to declining trends in patients without cancer, primary cardiovascular admissions in patients with cancer is increasing. The highest admission rates are in patients with haematological cancer, and the most common cause of admission is heart failure.
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BOLD cofluctuation 'events' are predicted from static functional connectivity.

Open Access Issue N/A Vol 260 Published on 2022-10-01 PMID 35842100 PMCID PMC9428936
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Keywords: Networks, Simulations, Resting-state Fmri, Events, Rsfc, Cofluctuations
DOI: https://doi.org/10.1016/j.neuroimage.2022.119476
Authors: Zach Ladwig In X Benjamin A Seitzman In X Ally Dworetsky In X Yuhua Yu In X Babatunde Adeyemo In X Derek M Smith In X Steven E Petersen In X Caterina Gratton In X
Abstract: Recent work identified single time points ("events") of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or if it could arise from sampling variability alone. First, we show that events are not discrete - there is a gradually increasing relationship between network structure and cofluctuation; ∼50% of samples show very strong network structure. Second, using simulations we show that this relationship is predicted from sampling variability on static FC. Finally, we show that randomly selected points can capture network structure about as well as events, largely because of their temporal spacing. Together, these results suggest that, while events exhibit particularly strong representations of static FC, there is little evidence that events are unique timepoints that drive FC structure. Instead, a parsimonious explanation for the data is that events arise from a single static, but noisy, FC structure.
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Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.

Open Access Issue 11 Vol 23 Published on 2022-10-01 PMID 35640889 PMCID PMC9584621
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Keywords: Arterial stiffness, Cardiovascular Magnetic Resonance, Left ventricle, Pericardial Fat, Left Atrium, Cardiometabolic Disease
DOI: https://doi.org/10.1093/ehjci/jeac101
Authors: Maddalena Ardissino In X Celeste McCracken In X Andrew Bard In X Charalambos Antoniades In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Aims

We evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants.

Methods and results

We extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.

Conclusion

We demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.
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Cardiovascular Magnetic Resonance Tissue Characterization by T1 and T2 Mapping: A Moving Target in Need of Stable References.

Issue 9 Vol 15 Published on 2022-09-01 PMID 36126129 PMCID N/A
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Keywords: Myocardium, Magnetic resonance, epidemiology, risk factors, Editorials
DOI: https://doi.org/10.1161/circimaging.122.014743
Authors: Michael Jerosch-Herold In X Steffen E Petersen In X
Abstract: No Abstract Available
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Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response.

Open Access Issue 9 Vol 2 Published on 2022-09-01 PMID 35975199 PMCID PMC9372021
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Keywords: Mass spectrometry, Proteomics, Vaccination, Covid-19, Sars-cov-2, Variant Of Concern, Delta Variant, Omicron Variant, Complement: Immunoglobulin
DOI: https://doi.org/10.1016/j.crmeth.2022.100279
Authors: Ivan Doykov In X Tomas Baldwin In X Justyna Spiewak In X Kimberly C Gilmour In X Joseph M Gibbons In X Corinna Pade In X Catherine J Reynolds In X Áine McKnight In X Mahdad Noursadeghi In X Mala K Maini In X Charlotte Manisty In X Thomas Treibel In X Gabriella Captur In X Marianna Fontana In X Rosemary J Boyton In X Daniel M Altmann In X Tim Brooks In X Amanda Semper In X In X James C Moon In X Kevin Mills In X Wendy E Heywood In X
Abstract: Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.
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Corrigendum to: Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.

Open Access Issue 9 Vol 23 Published on 2022-08-01 PMID 35703377 PMCID PMC9365303
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jeac119
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Dorina Gabriela Condurache In X Nay Aung In X Jose D Vargas In X Hafiz Naderi In X Patricia B Munroe In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract: No Abstract Available
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Automatic 3D+t four-chamber CMR quantification of the UK biobank: integrating imaging and non-imaging data priors at scale.

Issue N/A Vol 80 Published on 2022-08-01 PMID 35665663 PMCID N/A
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Keywords: Cardiac Mr, Uk Biobank, Statistical Shape Models, Deep Learning, Population Imaging, Fully Automatic Analysis, Cardiac Functional Indexes, Cardiac Morphological Analysis
DOI: https://doi.org/10.1016/j.media.2022.102498
Authors: Yan Xia In X Xiang Chen In X Nishant Ravikumar In X Christopher Kelly In X Rahman Attar In X Nay Aung In X Stefan Neubauer In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: Accurate 3D modelling of cardiac chambers is essential for clinical assessment of cardiac volume and function, including structural, and motion analysis. Furthermore, to study the correlation between cardiac morphology and other patient information within a large population, it is necessary to automatically generate cardiac mesh models of each subject within the population. In this study, we introduce MCSI-Net (Multi-Cue Shape Inference Network), where we embed a statistical shape model inside a convolutional neural network and leverage both phenotypic and demographic information from the cohort to infer subject-specific reconstructions of all four cardiac chambers in 3D. In this way, we leverage the ability of the network to learn the appearance of cardiac chambers in cine cardiac magnetic resonance (CMR) images, and generate plausible 3D cardiac shapes, by constraining the prediction using a shape prior, in the form of the statistical modes of shape variation learned a priori from a subset of the population. This, in turn, enables the network to generalise to samples across the entire population. To the best of our knowledge, this is the first work that uses such an approach for patient-specific cardiac shape generation. MCSI-Net is capable of producing accurate 3D shapes using just a fraction (about 23% to 46%) of the available image data, which is of significant importance to the community as it supports the acceleration of CMR scan acquisitions. Cardiac MR images from the UK Biobank were used to train and validate the proposed method. We also present the results from analysing 40,000 subjects of the UK Biobank at 50 time-frames, totalling two million image volumes. Our model can generate more globally consistent heart shape than that of manual annotations in the presence of inter-slice motion and shows strong agreement with the reference ranges for cardiac structure and function across cardiac ventricles and atria.
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Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.

Open Access Issue 9 Vol 23 Published on 2022-08-01 PMID 34907415 PMCID PMC9365306
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Keywords: Mortality, Atrial fibrillation, Stroke, Ischaemic Heart Disease, Cardiovascular Magnetic Resonance, Left ventricle, Vascular Risk Factors, Cardiovascular Outcomes, Lef, T Atrium
DOI: https://doi.org/10.1093/ehjci/jeab266
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Dorina Condurache In X Nay Aung In X Jose D Vargas In X Hafiz Naderi In X Patricia B Munroe In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.
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Estimation of biological heart age using cardiovascular magnetic resonance radiomics.

Open Access Issue 1 Vol 12 Published on 2022-07-01 PMID 35896705 PMCID PMC9329281
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Keywords:
DOI: https://doi.org/10.1038/s41598-022-16639-9
Authors: Zahra Raisi-Estabragh In X Ahmed Salih In X Polyxeni Gkontra In X Angélica Atehortúa In X Petia Radeva In X Ilaria Boscolo Galazzo In X Gloria Menegaz In X Nicholas C Harvey In X Karim Lekadir In X Steffen E Petersen In X
Abstract: We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a "heart age delta", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.
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Minimising multi-centre radiomics variability through image normalisation: a pilot study.

Open Access Issue 1 Vol 12 Published on 2022-07-01 PMID 35869125 PMCID PMC9307565
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Keywords:
DOI: https://doi.org/10.1038/s41598-022-16375-0
Authors: Víctor M Campello In X Carlos Martín-Isla In X Cristian Izquierdo In X Andrea Guala In X José F Rodríguez Palomares In X David Viladés In X Martín L Descalzo In X Mahir Karakas In X Ersin Çavuş In X Zahra Raisi-Estabragh In X Steffen E Petersen In X Sergio Escalera In X Santi Seguí In X Karim Lekadir In X
Abstract: Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.
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Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.

Open Access Issue 7 Vol 19 Published on 2022-07-01 PMID 35834561 PMCID PMC9282660
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Keywords:
DOI: https://doi.org/10.1371/journal.pmed.1004039
Authors: Anya Topiwala In X Chaoyue Wang In X Klaus P Ebmeier In X Stephen Burgess In X Steven Bell In X Daniel F Levey In X Hang Zhou In X Celeste McCracken In X Adriana Roca-Fernández In X Steffen E Petersen In X Betty Raman In X Masud Husain In X Joel Gelernter In X Karla L Miller In X Stephen M Smith In X Thomas E Nichols In X
Abstract:

Background

Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.

Methods and findings

Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the "Snap" card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.

Conclusions

To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.
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Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy-Associated Putative Pathogenic Gene Variants in UK Biobank Participants.

Issue 2 Vol 146 Published on 2022-07-01 PMID 35708014 PMCID PMC9375305
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Keywords: Genetics, Genetic Testing, Arrhythmias, Cardiac, Penetrance, Cardiomyopathies, Death, Sudden, Cardiac
DOI: https://doi.org/10.1161/circulationaha.121.058143
Authors: Ravi A Shah In X Babken Asatryan In X Ghaith Sharaf Dabbagh In X Nay Aung In X Mohammed Y Khanji In X Luis R Lopes In X Stefan van Duijvenboden In X Anthony Holmes In X Daniele Muser In X Andrew P Landstrom In X Aaron Mark Lee In X Pankaj Arora In X Christopher Semsarian In X Virend K Somers In X Anjali T Owens In X Patricia B Munroe In X Steffen E Petersen In X C Anwar A Chahal In X In X
Abstract:

Background

There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features.

Methods

UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative.

Results

Among 18 665 individuals included in the study, 1463 (7.8%) possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes as compared with those with variants in moderate/limited evidence genes.

Conclusions

In the UK Biobank, ≈1 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.
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Our latest publication 'Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy-Associated Putative Pathogenic Gene Variants in UK Biobank Participants.' offers novel methodological insights from Shah et al:
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Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.

Open Access Issue 6603 Vol 377 Published on 2022-07-01 PMID 35699621 PMCID PMC9210451
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Keywords:
DOI: https://doi.org/10.1126/science.abq1841
Authors: Catherine J Reynolds In X Corinna Pade In X Joseph M Gibbons In X Ashley D Otter In X Kai-Min Lin In X Diana Muñoz Sandoval In X Franziska P Pieper In X David K Butler In X Siyi Liu In X George Joy In X Nasim Forooghi In X Thomas A Treibel In X Charlotte Manisty In X James C Moon In X In X In X Amanda Semper In X Tim Brooks In X Áine McKnight In X Daniel M Altmann In X Rosemary J Boyton In X Hakam Abbass In X Aderonke Abiodun In X Mashael Alfarih In X Zoe Alldis In X Daniel M Altmann In X Oliver E Amin In X Mervyn Andiapen In X Jessica Artico In X João B Augusto In X Georgina L Baca In X Sasha N L Bailey In X Anish N Bhuva In X Alex Boulter In X Ruth Bowles In X Rosemary J Boyton In X Olivia V Bracken In X Ben O'Brien In X Tim Brooks In X Natalie Bullock In X David K Butler In X Gabriella Captur In X Olivia Carr In X Nicola Champion In X Carmen Chan In X Aneesh Chandran In X Tom Coleman In X Jorge Couto de Sousa In X Xose Couto-Parada In X Eleanor Cross In X Teresa Cutino-Moguel In X Silvia D'Arcangelo In X Rhodri H Davies In X Brooke Douglas In X Cecilia Di Genova In X Keenan Dieobi-Anene In X Mariana O Diniz In X Anaya Ellis In X Karen Feehan In X Malcolm Finlay In X Marianna Fontana In X Nasim Forooghi In X Sasha Francis In X Joseph M Gibbons In X David Gillespie In X Derek Gilroy In X Matt Hamblin In X Gabrielle Harker In X Georgia Hemingway In X Jacqueline Hewson In X Wendy Heywood In X Lauren M Hickling In X Bethany Hicks In X Aroon D Hingorani In X Lee Howes In X Ivie Itua In X Victor Jardim In X Wing-Yiu Jason Lee In X Melaniepetra Jensen In X Jessica Jones In X Meleri Jones In X George Joy In X Vikas Kapil In X Caoimhe Kelly In X Hibba Kurdi In X Jonathan Lambourne In X Kai-Min Lin In X Siyi Liu In X Aaron Lloyd In X Sarah Louth In X Mala K Maini In X Vineela Mandadapu In X Charlotte Manisty In X Áine McKnight In X Katia Menacho In X Celina Mfuko In X Kevin Mills In X Sebastian Millward In X Oliver Mitchelmore In X Christopher Moon In X James Moon In X Diana Muñoz Sandoval In X Sam M Murray In X Mahdad Noursadeghi In X Ashley Otter In X Corinna Pade In X Susana Palma In X Ruth Parker In X Kush Patel In X Mihaela Pawarova In X Steffen E Petersen In X Brian Piniera In X Franziska P Pieper In X Lisa Rannigan In X Alicja Rapala In X Catherine J Reynolds In X Amy Richards In X Matthew Robathan In X Joshua Rosenheim In X Cathy Rowe In X Matthew Royds In X Jane Sackville West In X Genine Sambile In X Nathalie M Schmidt In X Hannah Selman In X Amanda Semper In X Andreas Seraphim In X Mihaela Simion In X Angelique Smit In X Michelle Sugimoto In X Leo Swadling In X Stephen Taylor In X Nigel Temperton In X Stephen Thomas In X George D Thornton In X Thomas A Treibel In X Art Tucker In X Ann Varghese In X Jessry Veerapen In X Mohit Vijayakumar In X Tim Warner In X Sophie Welch In X Hannah White In X Theresa Wodehouse In X Lucinda Wynne In X Dan Zahedi In X Benjamin Chain In X James C Moon In X
Abstract: The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
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Our new publication 'Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.' provides groundbreaking perspectives by Reynolds and team:
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Accuracy and reliability of diffusion imaging models.

Open Access Issue N/A Vol 254 Published on 2022-07-01 PMID 35339687 PMCID PMC9841915
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Keywords:
DOI: https://doi.org/10.1016/j.neuroimage.2022.119138
Authors: Nicole A Seider In X Babatunde Adeyemo In X Ryland Miller In X Dillan J Newbold In X Jacqueline M Hampton In X Kristen M Scheidter In X Jerrel Rutlin In X Timothy O Laumann In X Jarod L Roland In X David F Montez In X Andrew N Van In X Annie Zheng In X Scott Marek In X Benjamin P Kay In X G Larry Bretthorst In X Bradley L Schlaggar In X Deanna J Greene In X Yong Wang In X Steven E Petersen In X Deanna M Barch In X Evan M Gordon In X Abraham Z Snyder In X Joshua S Shimony In X Nico U F Dosenbach In X
Abstract: Diffusion imaging aims to non-invasively characterize the anatomy and integrity of the brain's white matter fibers. We evaluated the accuracy and reliability of commonly used diffusion imaging methods as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). Diffusion imaging methods that allow for crossing fibers (FSL's BedpostX [BPX], DSI Studio's Constant Solid Angle Q-Ball Imaging [CSA-QBI], MRtrix3's Constrained Spherical Deconvolution [CSD]) estimated excess fibers when insufficient data were present and/or when the data did not match the model priors. To reduce such overfitting, we developed a novel Bayesian Multi-tensor Model-selection (BaMM) method and applied it to the popular ball-and-stick model used in BedpostX within the FSL software package. BaMM was robust to overfitting and showed high reliability and the relatively best crossing-fiber accuracy with increasing amounts of diffusion data. Thus, sufficient data and an overfitting resistant analysis method enhance precision diffusion imaging. For potential clinical applications of diffusion imaging, such as neurosurgical planning and deep brain stimulation (DBS), the quantities of data required to achieve diffusion imaging reliability are lower than those needed for functional MRI.
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Radiation safety for cardiovascular computed tomography imaging in paediatric cardiology: a joint expert consensus document of the EACVI, ESCR, AEPC, and ESPR.

Issue 8 Vol 23 Published on 2022-07-01 PMID 35262687 PMCID N/A
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Keywords: Radiation protection, Children, Congenital heart disease, Radiation Exposure, Cct
DOI: https://doi.org/10.1093/ehjci/jeac048
Authors: Marco Francone In X Alessia Gimelli In X Ricardo P J Budde In X Pablo Caro-Dominguez In X Andrew J Einstein In X Matthias Gutberlet In X Pal Maurovich-Horvat In X Owen Miller In X Eszter Nagy In X Luigi Natale In X Charles Peebles In X Steffen E Petersen In X Thomas Semple In X Israel Valverde In X Inga Voges In X Aurelio Secinaro In X Giovanni Di Salvo In X
Abstract: Children with congenital and acquired heart disease may be exposed to relatively high lifetime cumulative doses of ionizing radiation from necessary medical invasive and non-invasive imaging procedures. Although these imaging procedures are all essential to the care of these complex paediatric population and have contributed to meaningfully improved outcomes in these patients, exposure to ionizing radiation is associated with potential risks, including an increased lifetime attributable risk of cancer. The goal of this manuscript is to provide a comprehensive review of radiation dose management and cardiac computed tomography performance in the paediatric population with congenital and acquired heart disease, to encourage informed imaging to achieve indication-appropriate study quality at the lowest achievable dose.
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Breakthrough research 'Radiation safety for cardiovascular computed tomography imaging in paediatric cardiology: a joint expert consensus document of the EACVI, ESCR, AEPC, and ESPR.' by Francone & team reshapes scientific understanding:
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Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function.

Issue 6 Vol 54 Published on 2022-06-01 PMID 35697868 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1038/s41588-022-01083-2
Authors: Nay Aung In X Jose D Vargas In X Chaojie Yang In X Kenneth Fung In X Mihir M Sanghvi In X Stefan K Piechnik In X Stefan Neubauer In X Ani Manichaikul In X Jerome I Rotter In X Kent D Taylor In X Joao A C Lima In X David A Bluemke In X Steven M Kawut In X Steffen E Petersen In X Patricia B Munroe In X
Abstract: Right ventricular (RV) structure and function influence the morbidity and mortality from coronary artery disease (CAD), dilated cardiomyopathy (DCM), pulmonary hypertension and heart failure. Little is known about the genetic basis of RV measurements. Here we perform genome-wide association analyses of four clinically relevant RV phenotypes (RV end-diastolic volume, RV end-systolic volume, RV stroke volume, RV ejection fraction) from cardiovascular magnetic resonance images, using a state-of-the-art deep learning algorithm in 29,506 UK Biobank participants. We identify 25 unique loci associated with at least one RV phenotype at P < 2.27 ×10-8, 17 of which are validated in a combined meta-analysis (n = 41,830). Several candidate genes overlap with Mendelian cardiomyopathy genes and are involved in cardiac muscle contraction and cellular adhesion. The RV polygenic risk scores (PRSs) are associated with DCM and CAD. The findings substantially advance our understanding of the genetic underpinning of RV measurements.
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European Society of Cardiology: cardiovascular disease statistics 2021: Executive Summary.

Issue 4 Vol 8 Published on 2022-06-01 PMID 35488372 PMCID N/A
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Keywords: Mortality, Morbidity, Statistics, Cardiovascular disease, risk factors, Service Provision, European Society Of Cardiology, Health Infrastructure
DOI: https://doi.org/10.1093/ehjqcco/qcac014
Authors: Adam Timmis In X Panos Vardas In X Nick Townsend In X Aleksandra Torbica In X Hugo Katus In X Delphine De Smedt In X Chris P Gale In X Aldo P Maggioni In X Steffen E Petersen In X Radu Huculeci In X Dzianis Kazakiewicz In X Victor de Benito Rubio In X Barbara Ignatiuk In X Zahra Raisi-Estabragh In X Agnieszka Pawlak In X Efstratios Karagiannidis In X Roderick Treskes In X Dan Gaita In X John F Beltrame In X Alex McConnachie In X Isabel Bardinet In X Ian Graham In X Marcus Flather In X Perry Elliott In X Elias A Mossialos In X Franz Weidinger In X Stephan Achenbach In X
Abstract:

Aims

This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries.

Methods and results

Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, leftsided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures.

Conclusion

Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.
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Breakthrough research 'European Society of Cardiology: cardiovascular disease statistics 2021: Executive Summary.' by Timmis & team reshapes scientific understanding:
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Right ventricular longitudinal strain in the clinical routine: a state-of-the-art review.

Issue 7 Vol 23 Published on 2022-06-01 PMID 35147667 PMCID N/A
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Keywords: Reference values, Echocardiography, Pulmonary hypertension, Heart Failure, Heart valve diseases, Right Ventricle, Systemic Sclerosis, Speckle Tracking Echocardiography, Cardiac Magnetic Resonance, Cardiomyopathies, Right Ventricular Mechanics, Free Wall Longitudinal Strain, Congenital Heart Diseases
DOI: https://doi.org/10.1093/ehjci/jeac022
Authors: Denisa Muraru In X Kristina Haugaa In X Erwan Donal In X Ivan Stankovic In X Ivan Stankovic In X Jens Uwe Voigt In X Jens Uwe Voigt In X Steffen E Petersen In X Bogdan A Popescu In X Thomas Marwick In X
Abstract: Myocardial deformation imaging is a very attractive clinical tool for the assessment of right ventricular (RV) systolic performance, providing incremental diagnostic and prognostic information over the traditional indices of RV function. Among various imaging modalities, echocardiography is currently the method of choice for clinical assessment of RV longitudinal strain (RVLS). The methodology of 2D speckle-tracking echocardiography to obtain RVLS has been recently standardized and demonstrated to be feasible, accurate, and robust for clinical use. Inter-technique and inter-vendor comparability and reliability of RVLS are improving. RVLS is advantageous because it is more sensitive to subtle changes in myocardial function than conventional parameters used to assess RV function (i.e. tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction) representing a sensitive tool for the long-term follow-up of patients. Proper interpretation of measurements requires a deep understanding of RV mechanics and pathologic tissue characteristics in different cardiovascular conditions, as well as the influence of loading conditions, image properties, and tracking algorithms on RVLS measurements.
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Delighted to announce our latest publication 'Right ventricular longitudinal strain in the clinical routine: a state-of-the-art review.' by Muraru et al:
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Reply to Stöllberger et al.

Issue 6 Vol 240 Published on 2022-06-01 PMID 35106781 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1111/joa.13625
Authors: Bjarke Jensen In X Gustav J Strijkers In X Steffen E Petersen In X Mary N Sheppard In X Roelof-Jan Oostra In X Vincent M Christoffels In X
Abstract: No Abstract Available
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Honored to contribute to this publication: 'Reply to Stöllberger et al.'. Incredible collaboration with Jensen et al. Check it out:
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Individualized Functional Subnetworks Connect Human Striatum and Frontal Cortex.

Issue 13 Vol 32 Published on 2022-06-01 PMID 34718460 PMCID PMC9247416
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Keywords: fMRI, Striatum, Functional Connectivity, Brain Networks, Individual Variability
DOI: https://doi.org/10.1093/cercor/bhab387
Authors: Evan M Gordon In X Timothy O Laumann In X Scott Marek In X Dillan J Newbold In X Jacqueline M Hampton In X Nicole A Seider In X David F Montez In X Ashley M Nielsen In X Andrew N Van In X Annie Zheng In X Ryland Miller In X Joshua S Siegel In X Benjamin P Kay In X Abraham Z Snyder In X Deanna J Greene In X Bradley L Schlaggar In X Steven E Petersen In X Steven M Nelson In X Nico U F Dosenbach In X
Abstract: The striatum and cerebral cortex are interconnected via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate corticostriatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited in part by the practice of averaging neuroimaging data across individuals. Here we utilized highly sampled resting-state functional connectivity MRI for individual-specific precision functional mapping (PFM) of corticostriatal connections. We identified ten individual-specific subnetworks linking cortex-predominately frontal cortex-to striatum, most of which converged with nonhuman primate tract-tracing work. These included separable connections between nucleus accumbens core/shell and orbitofrontal/medial frontal gyrus; between anterior striatum and dorsomedial prefrontal cortex; between dorsal caudate and lateral prefrontal cortex; and between middle/posterior putamen and supplementary motor/primary motor cortex. Two subnetworks that did not converge with nonhuman primates were connected to cortical regions associated with human language function. Thus, precision subnetworks identify detailed, individual-specific, neurobiologically plausible corticostriatal connectivity that includes human-specific language networks.
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Publisher Correction: Reproducible brain-wide association studies require thousands of individuals.

Open Access Issue 7911 Vol 605 Published on 2022-05-01 PMID 35534626 PMCID PMC9132768
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Keywords:
DOI: https://doi.org/10.1038/s41586-022-04692-3
Authors: Scott Marek In X Brenden Tervo-Clemmens In X Finnegan J Calabro In X David F Montez In X Benjamin P Kay In X Alexander S Hatoum In X Meghan Rose Donohue In X William Foran In X Ryland L Miller In X Timothy J Hendrickson In X Stephen M Malone In X Sridhar Kandala In X Eric Feczko In X Oscar Miranda-Dominguez In X Alice M Graham In X Eric A Earl In X Anders J Perrone In X Michaela Cordova In X Olivia Doyle In X Lucille A Moore In X Gregory M Conan In X Johnny Uriarte In X Kathy Snider In X Benjamin J Lynch In X James C Wilgenbusch In X Thomas Pengo In X Angela Tam In X Jianzhong Chen In X Dillan J Newbold In X Annie Zheng In X Nicole A Seider In X Andrew N Van In X Athanasia Metoki In X Roselyne J Chauvin In X Timothy O Laumann In X Deanna J Greene In X Steven E Petersen In X Hugh Garavan In X Wesley K Thompson In X Thomas E Nichols In X B T Thomas Yeo In X Deanna M Barch In X Beatriz Luna In X Damien A Fair In X Nico U F Dosenbach In X
Abstract: No Abstract Available
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Honored to contribute to this publication: 'Publisher Correction: Reproducible brain-wide association studies require thousands of individuals.'. Incredible collaboration with Marek et al. Check it out:
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Investigation of Carboxylic Acid Isosteres and Prodrugs for Inhibition of the Human SIRT5 Lysine Deacylase Enzyme.

Open Access Issue 22 Vol 61 Published on 2022-05-01 PMID 35299278 PMCID PMC9315039
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Keywords: Enzyme inhibitors, Prodrugs, Sirtuins, Sirt5, Bioisosteres
DOI: https://doi.org/10.1002/anie.202115805
Authors: Nima Rajabi In X Tobias N Hansen In X Alexander L Nielsen In X Huy T Nguyen In X Michael Baek In X Julie E Bolding In X Oskar Ø Bahlke In X Sylvester E G Petersen In X Christian R O Bartling In X Kristian Strømgaard In X Christian A Olsen In X
Abstract: Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing ϵ-N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but potent compounds with activity in cells have been lacking. Here we developed mechanism-based inhibitors that incorporate isosteres of a carboxylic acid residue that is important for high-affinity binding to the enzyme active site. By masking of the tetrazole moiety of the most potent candidate from our initial SAR study, we achieved potent and cytoselective growth inhibition for the treatment of SIRT5-dependent leukemic cancer cell lines in culture. Thus, we provide an efficient, cellularly active small molecule that targets SIRT5, which can help elucidate its function and potential as a future drug target. This work shows that masked isosteres of carboxylic acids are viable chemical motifs for the development of inhibitors that target mitochondrial enzymes, which may have applications beyond the sirtuin field.
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HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.

Open Access Issue 1 Vol 166 Published on 2022-05-01 PMID 35156709 PMCID PMC9111350
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Keywords: Vaccine, HLA, immunogenetics, T-cell Immunity, Covid-19, Sars-cov-2
DOI: https://doi.org/10.1111/imm.13450
Authors: Stuart Astbury In X Catherine J Reynolds In X David K Butler In X Diana C Muñoz-Sandoval In X Kai-Min Lin In X Franziska P Pieper In X Ashley Otter In X Afroditi Kouraki In X Lola Cusin In X Jessica Nightingale In X Amrita Vijay In X Simon Craxford In X Guruprasad P Aithal In X Patrick J Tighe In X Joseph M Gibbons In X Corinna Pade In X George Joy In X Mala Maini In X Benny Chain In X Amanda Semper In X Timothy Brooks In X Benjamin J Ollivere In X Áine McKnight In X Mahdad Noursadeghi In X Thomas A Treibel In X Charlotte Manisty In X James C Moon In X In X Ana M Valdes In X Rosemary J Boyton In X Daniel M Altmann In X
Abstract: SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965.
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So excited to see our paper, 'HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.', in print! A great team effort with Astbury et al.:
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Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.

Issue 6 Vol 29 Published on 2022-05-01 PMID 35048949 PMCID N/A
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Keywords: Cardiac Magnetic Resonance, Cardiovascular Health, Coffee Consumption
DOI: https://doi.org/10.1093/eurjpc/zwac008
Authors: Judit Simon In X Kenneth Fung In X Zahra Raisi-Estabragh In X Nay Aung In X Mohammed Y Khanji In X Márton Kolossváry In X Béla Merkely In X Patricia B Munroe In X Nicholas C Harvey In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Pál Maurovich-Horvat In X
Abstract:

Aims

To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.

Methods and results

UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.

Conclusion

Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.
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Significant research milestone: 'Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.' published, demonstrating innovative approaches by Simon & team:
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Society for Cardiovascular Magnetic Resonance (SCMR) guidelines for reporting cardiovascular magnetic resonance examinations.

Open Access Issue 1 Vol 24 Published on 2022-04-01 PMID 35484555 PMCID PMC9052489
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Keywords:
DOI: https://doi.org/10.1186/s12968-021-00827-z
Authors: W Gregory Hundley In X David A Bluemke In X Jan Bogaert In X Scott D Flamm In X Marianna Fontana In X Matthias G Friedrich In X Lars Grosse-Wortmann In X Theodoros D Karamitsos In X Christopher M Kramer In X Raymond Y Kwong In X Michael McConnell In X Eike Nagel In X Stefan Neubauer In X Robin Nijveldt In X Dudley J Pennell In X Steffen E Petersen In X Subha V Raman In X Albert van Rossum In X
Abstract: No Abstract Available
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Sharing our latest publication, 'Society for Cardiovascular Magnetic Resonance (SCMR) guidelines for reporting cardiovascular magnetic resonance examinations.', with Hundley et al. Proud of what we achieved together:
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Cost-Minimization Analysis for Cardiac Revascularization in 12 Health Care Systems Based on the EuroCMR/SPINS Registries.

Issue 4 Vol 15 Published on 2022-04-01 PMID 35033498 PMCID N/A
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Keywords: CAD, Cost-effectiveness, Cmr, Stress Testing, Ffr
DOI: https://doi.org/10.1016/j.jcmg.2021.11.008
Authors: Karine Moschetti In X Raymond Y Kwong In X Steffen E Petersen In X Massimo Lombardi In X Jerome Garot In X Dan Atar In X Frank E Rademakers In X Lilia M Sierra-Galan In X Sophie Mavrogeni In X Kuncheng Li In X Juliano Lara Fernandes In X Steffen Schneider In X Christophe Pinget In X Yin Ge In X Panagiotis Antiochos In X Christina Deluigi In X Oliver Bruder In X Heiko Mahrholdt In X Juerg Schwitter In X
Abstract:

Objectives

The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR).

Background

Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high.

Methods

In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses.

Results

Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups).

Conclusions

In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups.
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Cardiovascular Magnetic Resonance for Patients With COVID-19.

Open Access Issue 4 Vol 15 Published on 2022-04-01 PMID 34656482 PMCID PMC8514168
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Keywords: Ischemia, Myocarditis, Myocardial injury, Cardiovascular Magnetic Resonance, Covid-19, Sars-cov-2, Multisystem Inflammatory Syndrome
DOI: https://doi.org/10.1016/j.jcmg.2021.08.021
Authors: Steffen E Petersen In X Matthias G Friedrich In X Tim Leiner In X Matthew D Elias In X Vanessa M Ferreira In X Maximilian Fenski In X Scott D Flamm In X Mark Fogel In X Ria Garg In X Marc K Halushka In X Allison G Hays In X Nadine Kawel-Boehm In X Christopher M Kramer In X Eike Nagel In X Ntobeko A B Ntusi In X Ellen Ostenfeld In X Dudley J Pennell In X Zahra Raisi-Estabragh In X Scott B Reeder In X Carlos E Rochitte In X Jitka Starekova In X Dominika Suchá In X Qian Tao In X Jeanette Schulz-Menger In X David A Bluemke In X
Abstract: COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19-related myocarditis is likely infrequent, COVID-19-related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post-COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19-related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19.
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Associations of cognitive performance with cardiovascular magnetic resonance phenotypes in the UK Biobank.

Open Access Issue 5 Vol 23 Published on 2022-04-01 PMID 33987659 PMCID PMC9016359
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Keywords: Brain, Cognition, Cardiovascular disease, Dementia, Cardiovascular Magnetic Resonance, Vascular Risk Factors, Heart–brain Axis
DOI: https://doi.org/10.1093/ehjci/jeab075
Authors: Zahra Raisi-Estabragh In X Amine M'Charrak In X Celeste McCracken In X Luca Biasiolli In X Maddalena Ardissino In X Elizabeth M Curtis In X Nay Aung In X Claudia K Suemoto In X Clare Mackay In X Sana Suri In X Thomas E Nichols In X Nicholas C Harvey In X Steffen E Petersen In X Stefan Neubauer In X
Abstract:

Aims

Existing evidence suggests links between brain and cardiovascular health. We investigated associations between cognitive performance and cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank, considering a range of potential confounders.

Methods and results

We studied 29 763 participants with CMR and cognitive testing, specifically, fluid intelligence (FI, 13 verbal-numeric reasoning questions), and reaction time (RT, a timed pairs matching exercise); both were considered continuous variables for modelling. We included the following CMR metrics: left and right ventricular (LV and RV) volumes in end-diastole and end-systole, LV/RV ejection fractions, LV/RV stroke volumes, LV mass, and aortic distensibility. Multivariable linear regression models were used to estimate the association of each CMR measure with FI and RT, adjusting for age, sex, smoking, education, deprivation, diabetes, hypertension, high cholesterol, prior myocardial infarction, alcohol intake, and exercise level. We report standardized beta-coefficients, 95% confidence intervals, and P-values adjusted for multiple testing. In this predominantly healthy cohort (average age 63.0 ± 7.5 years), better cognitive performance (higher FI, lower RT) was associated with larger LV/RV volumes, higher LV/RV stroke volumes, greater LV mass, and greater aortic distensibility in fully adjusted models. There was some evidence of non-linearity in the relationship between FI and LV end-systolic volume, with reversal of the direction of association at very high volumes. Associations were consistent for men and women and in different ages.

Conclusion

Better cognitive performance is associated with CMR measures likely representing a healthier cardiovascular phenotype. These relationships remained significant after adjustment for a range of cardiometabolic, lifestyle, and demographic factors, suggesting possible involvement of alternative disease mechanisms.
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Reproducible brain-wide association studies require thousands of individuals.

Open Access Issue 7902 Vol 603 Published on 2022-03-01 PMID 35296861 PMCID PMC8991999
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Keywords:
DOI: https://doi.org/10.1038/s41586-022-04492-9
Authors: Scott Marek In X Brenden Tervo-Clemmens In X Finnegan J Calabro In X David F Montez In X Benjamin P Kay In X Alexander S Hatoum In X Meghan Rose Donohue In X William Foran In X Ryland L Miller In X Timothy J Hendrickson In X Stephen M Malone In X Sridhar Kandala In X Eric Feczko In X Oscar Miranda-Dominguez In X Alice M Graham In X Eric A Earl In X Anders J Perrone In X Michaela Cordova In X Olivia Doyle In X Lucille A Moore In X Gregory M Conan In X Johnny Uriarte In X Kathy Snider In X Benjamin J Lynch In X James C Wilgenbusch In X Thomas Pengo In X Angela Tam In X Jianzhong Chen In X Dillan J Newbold In X Annie Zheng In X Nicole A Seider In X Andrew N Van In X Athanasia Metoki In X Roselyne J Chauvin In X Timothy O Laumann In X Deanna J Greene In X Steven E Petersen In X Hugh Garavan In X Wesley K Thompson In X Thomas E Nichols In X B T Thomas Yeo In X Deanna M Barch In X Beatriz Luna In X Damien A Fair In X Nico U F Dosenbach In X
Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.
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AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.

Open Access Issue 3 Vol 12 Published on 2022-03-01 PMID 35296488 PMCID PMC8928293
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Keywords: Ophthalmology, Health Informatics, Medical Retina, Medical Ophthalmology
DOI: https://doi.org/10.1136/bmjopen-2021-058552
Authors: Siegfried Karl Wagner In X Fintan Hughes In X Mario Cortina-Borja In X Nikolas Pontikos In X Robbert Struyven In X Xiaoxuan Liu In X Hugh Montgomery In X Daniel C Alexander In X Eric Topol In X Steffen Erhard Petersen In X Konstantinos Balaskas In X Jack Hindley In X Axel Petzold In X Jugnoo S Rahi In X Alastair K Denniston In X Pearse A Keane In X
Abstract:

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.
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Precision measurement of cardiac structure and function in cardiovascular magnetic resonance using machine learning.

Open Access Issue 1 Vol 24 Published on 2022-03-01 PMID 35272664 PMCID PMC8908603
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Keywords: Image processing, Ventricular function, Machine Learning, Cardiac Magnetic Resonance, Cardiovascular Imaging
DOI: https://doi.org/10.1186/s12968-022-00846-4
Authors: Rhodri H Davies In X João B Augusto In X Anish Bhuva In X Hui Xue In X Thomas A Treibel In X Yang Ye In X Rebecca K Hughes In X Wenjia Bai In X Clement Lau In X Hunain Shiwani In X Marianna Fontana In X Rebecca Kozor In X Anna Herrey In X Luis R Lopes In X Viviana Maestrini In X Stefania Rosmini In X Steffen E Petersen In X Peter Kellman In X Daniel Rueckert In X John P Greenwood In X Gabriella Captur In X Charlotte Manisty In X Erik Schelbert In X James C Moon In X
Abstract:

Background

Measurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis.

Methods

A fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm ('machine') performance was compared to three clinicians ('human') and a commercial tool (cvi42, Circle Cardiovascular Imaging).

Findings

Machine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P < 0.05), translating to a 46% reduction in required trial sample size using an LVEF endpoint.

Conclusion

We present a fully automated algorithm for measuring LV structure and global systolic function that betters human performance for speed and precision.
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EACVI survey on burnout amongst cardiac imaging specialists during the 2019 coronavirus disease pandemic.

Open Access Issue 4 Vol 23 Published on 2022-03-01 PMID 35061874 PMCID PMC8807202
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Keywords: Burnout, Covid-19
DOI: https://doi.org/10.1093/ehjci/jeac002
Authors: Shruti S Joshi In X Ivan Stankovic In X Ahmet Demirkiran In X Kristina Haugaa In X Pal Maurovich-Horvat In X Bogdan A Popescu In X Bernard Cosyns In X Thor Edvardsen In X Steffen E Petersen In X Ricardo Fontes Carvalho In X Matteo Cameli In X Marc R Dweck In X
Abstract:

Aims

The European Association of Cardiovascular Imaging Scientific Initiatives Committee conducted a global survey to evaluate the impact of the 2019 coronavirus disease (COVID-19) pandemic on the mental well-being of cardiac imaging specialists.

Methods and results

In a prospective international survey performed between 23 July 2021 and 31 August 2021, we assessed the mental well-being of cardiac imaging specialists ∼18 months into the COVID-19 pandemic. One-hundred-and-twenty-five cardiac imaging specialists from 34 countries responded to the survey. More than half described feeling anxious during the pandemic, 34% felt melancholic, 27% felt fearful, and 23% respondents felt lonely. A quarter of respondents had increased their alcohol intake and more than half reported difficulties in sleeping. Two-thirds of respondents described worsening features of burnout during the past 18 months, 44% considered quitting their job. One in twenty respondents had experienced suicidal ideation during the pandemic. Despite these important issues, the majority of participants (57%) reported having no access to any formal mental health support at work.

Conclusion

The survey has highlighted important issues regarding the mental well-being of cardiac imaging specialists during the COVID-19 pandemic. This is a major issue in our sub-specialty, which requires urgent action and prioritization so that we can improve the mental health of cardiovascular imaging specialists.
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Aortic regurgitation management: a systematic review of clinical practice guidelines and recommendations.

Issue 2 Vol 8 Published on 2022-03-01 PMID 35026012 PMCID N/A
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Keywords: Aortic valve, Systematic review, Guidelines, Valvular Heart Disease, Aortic Regurgitation
DOI: https://doi.org/10.1093/ehjqcco/qcac001
Authors: Victor Galusko In X George Thornton In X Csilla Jozsa In X Baskar Sekar In X Dincer Aktuerk In X Thomas A Treibel In X Steffen E Petersen In X Adrian Ionescu In X Fabrizio Ricci In X Mohammed Y Khanji In X
Abstract: Guidelines for the diagnosis and management of aortic regurgitation (AR) contain recommendations that do not always match. We systematically reviewed clinical practice guidelines and summarized similarities and differences in the recommendations as well as gaps in evidence on the management of AR. We searched MEDLINE and Embase (1 January 2011 to 1 September 2021), Google Scholar, and websites of relevant organizations for contemporary guidelines that were rigorously developed as assessed by the Appraisal of Guidelines for Research and Evaluation II tool. Three guidelines met our inclusion criteria. There was consensus on the definition of severe AR and use of echocardiography and of multimodality imaging for diagnosis, with emphasis on comprehensive assessment by the heart valve team to assess suitability and choice of intervention. Surgery is indicated in all symptomatic patients and aortic valve replacement is the cornerstone of treatment. There is consistency in the frequency of follow-up of patients, and safety of non-cardiac surgery in patients without indications for surgery. Discrepancies exist in recommendations for 3D imaging and the use of global longitudinal strain and biomarkers. Cut-offs for left ventricular ejection fraction and size for recommending surgery in severe asymptomatic AR also vary. There are no specific AR cut-offs for high-risk surgery and the role of percutaneous intervention is yet undefined. Recommendations on the treatment of mixed valvular disease are sparse and lack robust prospective data.
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Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.

Open Access Issue 1 Vol 12 Published on 2022-02-01 PMID 35165324 PMCID PMC8844403
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Keywords:
DOI: https://doi.org/10.1038/s41598-022-06315-3
Authors: Bogdan A Gheorghiță In X Lucian M Itu In X Puneet Sharma In X Constantin Suciu In X Jens Wetzl In X Christian Geppert In X Mohamed Ali Asik Ali In X Aaron M Lee In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Jeanette Schulz-Menger In X Teodora Chițiboi In X
Abstract: Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.
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Towards range-guidance in proton therapy to detect organ motion-induced dose degradations.

Issue 2 Vol 8 Published on 2022-02-01 PMID 35108695 PMCID N/A
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Keywords: Proton Therapy, Advanced Prostate Cancer, Water Equivalent Path Length, Range-guidance, Inter-fractional Motion
DOI: https://doi.org/10.1088/2057-1976/ac5151
Authors: Kia Busch In X Andreas G Andersen In X Jørgen B B Petersen In X Stine E Petersen In X Heidi S Rønde In X Lise Bentzen In X Sara Pilskog In X Peter Skyt In X Ole Nørrevang In X Ludvig P Muren In X
Abstract: Introduction.Internal organ motion and deformations may cause dose degradations in proton therapy (PT) that are challenging to resolve using conventional image-guidance strategies. This study aimed to investigate the potential ofrange guidanceusing water-equivalent path length (WEPL) calculations to detect dose degradations occurring in PT.Materials and methods. Proton ranges were estimated using WEPL calculations. Field-specific isodose surfaces in the planning CT (pCT), from robustly optimised five-field proton plans (opposing lateral and three posterior/posterior oblique beams) for locally advanced prostate cancer patients, were used as starting points. WEPLs to each point on the field-specific isodoses in the pCT were calculated. The corresponding range for each point was found in the repeat CTs (rCTs). The spatial agreement between the resulting surfaces in the rCTs (hereafter referred to as iso-WEPLs) and the isodoses re-calculated in rCTs was evaluated for different dose levels and Hausdorff thresholds (2-5 mm). Finally, the sensitivity and specificity of detecting target dose degradation (V95% < 95%) using spatial agreement measures between the iso-WEPLs and isodoses in the pCT was evaluated.Results. The spatial agreement between the iso-WEPLs and isodoses in the rCTs depended on the Hausdorff threshold. The agreement was 65%-88% for a 2 mm threshold, 83%-96% for 3 mm, 90%-99% for 4 mm, and 94%-99% for 5 mm, across all fields and isodose levels. Minor differences were observed between the different isodose levels investigated. Target dose degradations were detected with 82%-100% sensitivity and 75%-80% specificity using a 2 mm Hausdorff threshold for the lateral fields.Conclusion. Iso-WEPLs were comparable to isodoses re-calculated in the rCTs. The proposed strategy could detect target dose degradations occurring in the rCTs and could be an alternative to a fully-fledged dose re-calculation to detect anatomical variations severely influencing the proton range.
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European Society of Cardiology: cardiovascular disease statistics 2021.

Issue 8 Vol 43 Published on 2022-02-01 PMID 35016208 PMCID N/A
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Keywords: Mortality, Morbidity, Statistics, Cardiovascular disease, risk factors, Service Provision, European Society Of Cardiology, Health Infrastructure
DOI: https://doi.org/10.1093/eurheartj/ehab892
Authors: Adam Timmis In X Panos Vardas In X Nick Townsend In X Aleksandra Torbica In X Hugo Katus In X Delphine De Smedt In X Chris P Gale In X Aldo P Maggioni In X Steffen E Petersen In X Radu Huculeci In X Dzianis Kazakiewicz In X Victor de Benito Rubio In X Barbara Ignatiuk In X Zahra Raisi-Estabragh In X Agnieszka Pawlak In X Efstratios Karagiannidis In X Roderick Treskes In X Dan Gaita In X John F Beltrame In X Alex McConnachie In X Isabel Bardinet In X Ian Graham In X Marcus Flather In X Perry Elliott In X Elias A Mossialos In X Franz Weidinger In X Stephan Achenbach In X In X
Abstract:

Aims

This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries.

Methods and results

Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, left-sided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures.

Conclusion

Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.
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Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.

Issue 2 Vol 61 Published on 2022-02-01 PMID 34632922 PMCID N/A
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Keywords: Breast Cancer; Proton Therapy; Treatment Planning; Plan Evaluation
DOI: https://doi.org/10.1080/0284186x.2021.1986229
Authors: Maria Fuglsang Jensen In X Line Bjerregaard Stick In X Morten Høyer In X Camilla Jensenius Skovhus Kronborg In X Ebbe Laugaard Lorenzen In X Hanna Rahbek Mortensen In X Petra Witt Nyström In X Stine Elleberg Petersen In X Pia Randers In X Linh My Hoang Thai In X Esben Svitzer Yates In X Birgitte Vrou Offersen In X
Abstract:

Background

The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark.

Material and methods

Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes.

Results

The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five.

Conclusion

This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.
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Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation.

Open Access Issue 2 Vol 240 Published on 2022-02-01 PMID 34569075 PMCID PMC8742974
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Keywords: Heart, Cardiomyopathy, Magnetic Resonance Imaging, Noncompaction
DOI: https://doi.org/10.1111/joa.13559
Authors: Hanne C E Riekerk In X Bram F Coolen In X Gustav J Strijkers In X Allard C van der Wal In X Steffen E Petersen In X Mary N Sheppard In X Roelof-Jan Oostra In X Vincent M Christoffels In X Bjarke Jensen In X
Abstract: The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre-test probability, diagnosis left ventricular noncompaction cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post-natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non-invasive imaging. Using macroscopy, histology and low- and high-resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation-negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation-negative when assessed with MRI-based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.
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2021 ESC Guidelines on cardiovascular disease prevention in clinical practice.

Issue 1 Vol 29 Published on 2022-02-01 PMID 34558602 PMCID N/A
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Keywords: Population, Lipids, Air pollution, Climate change, Blood pressure, Nutrition, Diabetes, Prevention, Smoking, Psychosocial factors, risk management, Guidelines, Risk Estimation, Shared Decision-making, Healthy Lifestyle, Lifetime Risk, Personalized, Stepwise Approach, Lifetime Benefit
DOI: https://doi.org/10.1093/eurjpc/zwab154
Authors: Frank L J Visseren In X François Mach In X Yvo M Smulders In X David Carballo In X Konstantinos C Koskinas In X Maria Bäck In X Athanase Benetos In X Alessandro Biffi In X José-Manuel Boavida In X Davide Capodanno In X Bernard Cosyns In X Carolyn Crawford In X Constantinos H Davos In X Ileana Desormais In X Emanuele Di Angelantonio In X Oscar H Franco In X Sigrun Halvorsen In X F D Richard Hobbs In X Monika Hollander In X Ewa A Jankowska In X Matthias Michal In X Simona Sacco In X Naveed Sattar In X Lale Tokgozoglu In X Serena Tonstad In X Konstantinos P Tsioufis In X Ineke van Dis In X Isabelle C van Gelder In X Christoph Wanner In X Bryan Williams In X In X
Abstract: No Abstract Available
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A phase I/II study of acute and late physician assessed and patient-reported morbidity following whole pelvic radiation in high-risk prostate cancer patients.

Issue 2 Vol 61 Published on 2022-02-01 PMID 34543143 PMCID N/A
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Keywords: Morbidity, Radiotherapy, Quality of life, prostate cancer, Patient-reported Outcomes
DOI: https://doi.org/10.1080/0284186x.2021.1979246
Authors: Stine E Petersen In X Lise B Thorsen In X Steinbjørn Hansen In X Peter M Petersen In X Henriette Lindberg In X Mette Moe In X Jørgen B Petersen In X Ludvig P Muren In X Morten Høyer In X Lise Bentzen In X
Abstract:

Background

The aim of this study was to assess acute and late morbidity measured by the physician and patient-reported outcomes (PROs) in high-risk prostate cancer (PC) patients receiving whole pelvic intensity-modulated radiotherapy (IMRT) in the setting of a national clinical trial.

Material and methods

A total of 88 patients with adenocarcinoma of the prostate and high-risk parameters were enrolled from 2011 to 2013. All patients received 78 Gy in 39 fractions of IMRT delivering simultaneous 78 Gy to the prostate and 56 Gy to the seminal vesicles and lymph nodes. Physician-reported morbidity was assessed by CTCAE v.4.0. PROs were registered for gastro-intestinal (GI) by the RT-ARD score, genito-urinary (GU) by DAN-PSS, sexual and hormonal by EPIC-26, and quality of life (QoL) by EORTC QLQ-C30.

Results

Median follow-up (FU) time was 4.6 years. No persistent late CTCAE grade 3+ morbidity was observed. Prevalence of CTCAE grade 2+ GI morbidities varied from 0 to 6% at baseline throughout FU time, except for diarrhea, which was reported in 19% of the patients post-RT. PROs revealed increased GI morbidity (≥1 monthly episode) for "rectal urgency", "use of pads", "incomplete evacuation", "mucus in stool" and "bowel function impact on QoL" all remained significantly different (p < .05) at 60 months compared to baseline. CTCAE grade 2+ GU and sexual morbidity were unchanged. GU PROs on obstructive and irritative GU items (≥daily episode) increased during RT and normalized at 24 months. No clinically significant differences were found in sexual, hormonal, and QoL scores compared to baseline.

Conclusions

Whole pelvic RT resulted in a mild to the moderate burden of late GI morbidities demonstrated by a relatively high prevalence of PROs. Whereas, physician-assessed morbidity revealed a low prevalence of late GI morbidity scores. This emphasizes the importance of using both PROs and physician-reported scoring scales when reporting late morbidity in clinical trials.
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Editorial: Insights in cardiovascular imaging: 2021.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 36684580 PMCID PMC9846317
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Keywords: Echocardiography, Machine Learning, Strain Imaging, Cardiac Magnetic Resonance Imaging, Computed Tomography Coronary Angiography, Plaque Characterization
DOI: https://doi.org/10.3389/fcvm.2022.1061337
Authors: Ramya Parasa In X Karl J Weiss In X Christos V Bourantas In X Steffen E Petersen In X Sebastian Kelle In X Ross J Thomson In X
Abstract: No Abstract Available
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Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 36426221 PMCID PMC9681217
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Keywords: Artificial intelligence, Trustworthiness, Cardiovascular Imaging, Machine Learning (Ml), Ai Risk
DOI: https://doi.org/10.3389/fcvm.2022.1016032
Authors: Liliana Szabo In X Zahra Raisi-Estabragh In X Ahmed Salih In X Celeste McCracken In X Esmeralda Ruiz Pujadas In X Polyxeni Gkontra In X Mate Kiss In X Pal Maurovich-Horvath In X Hajnalka Vago In X Bela Merkely In X Aaron M Lee In X Karim Lekadir In X Steffen E Petersen In X
Abstract: A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their "trustworthiness" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a "trustworthy AI system." We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.
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Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study.

Open Access Issue 11 Vol 17 Published on 2022-01-01 PMID 36399449 PMCID PMC9674175
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0277344
Authors: Ahmed Salih In X Ilaria Boscolo Galazzo In X Steffen E Petersen In X Karim Lekadir In X Petia Radeva In X Gloria Menegaz In X André Altmann In X
Abstract: Recent evidence suggests that shorter telomere length (TL) is associated with neuro degenerative diseases and aging related outcomes. The causal association between TL and brain characteristics represented by image derived phenotypes (IDPs) from different magnetic resonance imaging (MRI) modalities remains unclear. Here, we use two-sample Mendelian randomization (MR) to systematically assess the causal relationships between TL and 3,935 brain IDPs. Overall, the MR results suggested that TL was causally associated with 193 IDPs with majority representing diffusion metrics in white matter tracts. 68 IDPs were negatively associated with TL indicating that longer TL causes decreasing in these IDPs, while the other 125 were associated positively (longer TL leads to increased IDPs measures). Among them, ten IDPs have been previously reported as informative biomarkers to estimate brain age. However, the effect direction between TL and IDPs did not reflect the observed direction between aging and IDPs: longer TL was associated with decreases in fractional anisotropy and increases in axial, radial and mean diffusivity. For instance, TL was positively associated with radial diffusivity in the left perihippocampal cingulum tract and with mean diffusivity in right perihippocampal cingulum tract. Our results revealed a causal role of TL on white matter integrity which makes it a valuable factor to be considered when brain age is estimated and investigated.
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Cardiac aging synthesis from cross-sectional data with conditional generative adversarial networks.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 36211555 PMCID PMC9537599
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Keywords: Synthesis, Magnetic Resonance Imaging, Data Augmentation, Aging Heart, Generative Adversarial Network
DOI: https://doi.org/10.3389/fcvm.2022.983091
Authors: Víctor M Campello In X Tian Xia In X Xiao Liu In X Pedro Sanchez In X Carlos Martín-Isla In X Steffen E Petersen In X Santi Seguí In X Sotirios A Tsaftaris In X Karim Lekadir In X
Abstract: Age has important implications for health, and understanding how age manifests in the human body is the first step for a potential intervention. This becomes especially important for cardiac health, since age is the main risk factor for development of cardiovascular disease. Data-driven modeling of age progression has been conducted successfully in diverse applications such as face or brain aging. While longitudinal data is the preferred option for training deep learning models, collecting such a dataset is usually very costly, especially in medical imaging. In this work, a conditional generative adversarial network is proposed to synthesize older and younger versions of a heart scan by using only cross-sectional data. We train our model with more than 14,000 different scans from the UK Biobank. The induced modifications focused mainly on the interventricular septum and the aorta, which is consistent with the existing literature in cardiac aging. We evaluate the results by measuring image quality, the mean absolute error for predicted age using a pre-trained regressor, and demonstrate the application of synthetic data for counter-balancing biased datasets. The results suggest that the proposed approach is able to model realistic changes in the heart using only cross-sectional data and that these data can be used to correct age bias in a dataset.
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Predicting post-contrast information from contrast agent free cardiac MRI using machine learning: Challenges and methods.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 36051279 PMCID PMC9426684
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Keywords: contrast, Decision tree, Machine Learning, Cmr, support vector machines, Deep Learning, Contrast-free
DOI: https://doi.org/10.3389/fcvm.2022.894503
Authors: Musa Abdulkareem In X Asmaa A Kenawy In X Elisa Rauseo In X Aaron M Lee In X Alireza Sojoudi In X Alborz Amir-Khalili In X Karim Lekadir In X Alistair A Young In X Michael R Barnes In X Philipp Barckow In X Mohammed Y Khanji In X Nay Aung In X Steffen E Petersen In X
Abstract:

Objectives

Currently, administering contrast agents is necessary for accurately visualizing and quantifying presence, location, and extent of myocardial infarction (MI) with cardiac magnetic resonance (CMR). In this study, our objective is to investigate and analyze pre- and post-contrast CMR images with the goal of predicting post-contrast information using pre-contrast information only. We propose methods and identify challenges.

Methods

The study population consists of 272 retrospectively selected CMR studies with diagnoses of MI (n = 108) and healthy controls (n = 164). We describe a pipeline for pre-processing this dataset for analysis. After data feature engineering, 722 cine short-axis (SAX) images and segmentation mask pairs were used for experimentation. This constitutes 506, 108, and 108 pairs for the training, validation, and testing sets, respectively. We use deep learning (DL) segmentation (UNet) and classification (ResNet50) models to discover the extent and location of the scar and classify between the ischemic cases and healthy cases (i.e., cases with no regional myocardial scar) from the pre-contrast cine SAX image frames, respectively. We then capture complex data patterns that represent subtle signal and functional changes in the cine SAX images due to MI using optical flow, rate of change of myocardial area, and radiomics data. We apply this dataset to explore two supervised learning methods, namely, the support vector machines (SVM) and the decision tree (DT) methods, to develop predictive models for classifying pre-contrast cine SAX images as being a case of MI or healthy.

Results

Overall, for the UNet segmentation model, the performance based on the mean Dice score for the test set (n = 108) is 0.75 (±0.20) for the endocardium, 0.51 (±0.21) for the epicardium and 0.20 (±0.17) for the scar. For the classification task, the accuracy, F1 and precision scores of 0.68, 0.69, and 0.64, respectively, were achieved with the SVM model, and of 0.62, 0.63, and 0.72, respectively, with the DT model.

Conclusion

We have presented some promising approaches involving DL, SVM, and DT methods in an attempt to accurately predict contrast information from non-contrast images. While our initial results are modest for this challenging task, this area of research still poses several open problems.
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Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

Open Access Issue N/A Vol 16 Published on 2022-01-01 PMID 35916371 PMCID PMC9350522
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Keywords: hypertrophic cardiomyopathy, Pacemaker, Obstruction
DOI: https://doi.org/10.1177/17539447221108816
Authors: James W Malcolmson In X Rebecca K Hughes In X Abhishek Joshi In X Jackie Cooper In X Alexander Breitenstein In X Matthew Ginks In X Steffen E Petersen In X Saidi A Mohiddin In X Mehul B Dhinoja In X
Abstract:

Introduction

Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms.

Methods

Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed.

Results

Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1).

Conclusion

In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration.
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The Impact of Maternal Obesity on Offspring Cardiovascular Health: A Systematic Literature Review.

Open Access Issue N/A Vol 13 Published on 2022-01-01 PMID 35669689 PMCID PMC9164814
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Keywords: Obesity, Congenital heart disease, Cardiovascular disease, Maternal Obesity, Women’s Health, Cardiometabolic Disease, Lifecourse Epidemiology
DOI: https://doi.org/10.3389/fendo.2022.868441
Authors: Lois Kankowski In X Maddalena Ardissino In X Celeste McCracken In X Adam J Lewandowski In X Paul Leeson In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X Zahra Raisi-Estabragh In X
Abstract:

Objective

Obesity and cardiovascular disease are major global public health problems. Maternal obesity has been linked to multiple adverse health consequences for both mother and baby. Obesity during pregnancy may adversely alter the intrauterine environment, which has been hypothesised to predispose the offspring to poorer cardiovascular health throughout life. In this paper, we systematically review current literature examining the links between maternal obesity and offspring cardiovascular health.

Methods

This study is registered with PROSPERO (CRD42021278567) and was conducted in accordance with the PRISMA guidelines. A comprehensive systematic literature search was conducted, including two electronic databases (Ovid Medline, Embase), cross-referencing, author searching, and grey literature searches. We selected studies exploring the relationship between maternal obesity and offspring cardiovascular health, using pre-defined eligibility criteria. Studies were critically appraised using the ROBINS-I tool.

Results

From 1,214 results, 27 articles met the eligibility criteria. Multiple cardiovascular outcomes were considered, including congenital heart disease, cardiometabolic parameters, and cardiovascular diseases in neonates, children, and adults. In these studies, maternal obesity was consistently associated with congenital heart disease, several adverse cardiometabolic parameters throughout life including higher body mass index and insulin levels, and greater risk of cardiovascular disease in adulthood. Hypothesized underlying mechanisms are complex and multifactorial comprising genetic, environmental, and socioeconomic components, which can be difficult to quantify. Heterogeneity in study designs, highly selected study samples, and high risk of bias in some studies limit conclusions regarding causality.

Conclusions

We identified consistent evidence of links between maternal obesity and poorer offspring cardiovascular health throughout the lifecourse, extending from the neonatal period into adulthood. Although underlying mechanisms are unclear, our findings support consideration of targeted maternal obesity prevention for promotion of offspring cardiovascular health. This all-encompassing systematic review provides critical appraisal of the latest evidence, defines gaps and biases of existing literature, and may inform potential new public health strategies for cardiovascular disease prevention.

Systematic review registration

[https://www.crd.york.ac.uk/prospero], identifier PROSPERO (CRD42021278567).
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Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-Based Segmentation.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 35463778 PMCID PMC9021445
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Keywords: Segmentation, Cardiac Magnetic Resonance, Deep Learning, Fair Ai, Inequality Fairness In Deep Learning-Based Cmr Segmentation
DOI: https://doi.org/10.3389/fcvm.2022.859310
Authors: Esther Puyol-Antón In X Bram Ruijsink In X Jorge Mariscal Harana In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Reza Razavi In X Phil Chowienczyk In X Andrew P King In X
Abstract:

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias. The objective of this paper is to perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5 ± 7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

Results on the overall population showed an excellent agreement between the manual and automatic segmentations. We found statistically significant differences in Dice scores between races (white ∼94% vs. minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders. The results of a multivariate linear regression analysis showed that no covariate could explain the Dice score bias between racial groups. However, for the Mixed and Black race groups, sex showed a weak positive association with the Dice score. The results of an ANCOVA analysis showed that race was the main factor that can explain the overall difference in Dice scores between racial groups.

Conclusion

We have shown that racial bias can exist in DL-based cine CMR segmentation models when training with a database that is sex-balanced but not race-balanced such as the UK Biobank.
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Generalizable Framework for Atrial Volume Estimation for Cardiac CT Images Using Deep Learning With Quality Control Assessment.

Open Access Issue N/A Vol 9 Published on 2022-01-01 PMID 35155637 PMCID PMC8831539
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Keywords: Quality control, CT, Left Atrial Volume, Left Atrium, Deep Learning
DOI: https://doi.org/10.3389/fcvm.2022.822269
Authors: Musa Abdulkareem In X Mark S Brahier In X Fengwei Zou In X Alexandra Taylor In X Athanasios Thomaides In X Peter J Bergquist In X Monvadi B Srichai In X Aaron M Lee In X Jose D Vargas In X Steffen E Petersen In X
Abstract:

Objectives

Cardiac computed tomography (CCT) is a common pre-operative imaging modality to evaluate pulmonary vein anatomy and left atrial appendage thrombus in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). These images also allow for full volumetric left atrium (LA) measurement for recurrence risk stratification, as larger LA volume (LAV) is associated with higher recurrence rates. Our objective is to apply deep learning (DL) techniques to fully automate the computation of LAV and assess the quality of the computed LAV values.

Methods

Using a dataset of 85,477 CCT images from 337 patients, we proposed a framework that consists of several processes that perform a combination of tasks including the selection of images with LA from all other images using a ResNet50 classification model, the segmentation of images with LA using a UNet image segmentation model, the assessment of the quality of the image segmentation task, the estimation of LAV, and quality control (QC) assessment.

Results

Overall, the proposed LAV estimation framework achieved accuracies of 98% (precision, recall, and F1 score metrics) in the image classification task, 88.5% (mean dice score) in the image segmentation task, 82% (mean dice score) in the segmentation quality prediction task, and R 2 (the coefficient of determination) value of 0.968 in the volume estimation task. It correctly identified 9 out of 10 poor LAV estimations from a total of 337 patients as poor-quality estimates.

Conclusions

We proposed a generalizable framework that consists of DL models and computational methods for LAV estimation. The framework provides an efficient and robust strategy for QC assessment of the accuracy for DL-based image segmentation and volume estimation tasks, allowing high-throughput extraction of reproducible LAV measurements to be possible.
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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC.

Issue 1 Vol 24 Published on 2022-01-01 PMID 35083827 PMCID N/A
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Keywords: Transplantation, Diagnosis, Natriuretic peptides, Arrhythmias, Ejection fraction, Heart Failure, Hospitalization, Guidelines, Mechanical Circulatory Support, Pharmacotherapy, Acute Heart Failure, Cardiac Resynchronization Therapy, Multidisciplinary Management, Comorbidities, Advanced Heart Failure, Neuro-hormonal Antagonists
DOI: https://doi.org/10.1002/ejhf.2333
Authors: In X Theresa A McDonagh In X Marco Metra In X Marianna Adamo In X Roy S Gardner In X Andreas Baumbach In X Michael Böhm In X Haran Burri In X Javed Butler In X Jelena Čelutkienė In X Ovidiu Chioncel In X John G F Cleland In X Andrew J S Coats In X Maria G Crespo-Leiro In X Dimitrios Farmakis In X Martine Gilard In X Stephane Heymans In X Arno W Hoes In X Tiny Jaarsma In X Ewa A Jankowska In X Mitja Lainscak In X Carolyn S P Lam In X Alexander R Lyon In X John J V McMurray In X Alexandre Mebazaa In X Richard Mindham In X Claudio Muneretto In X Massimo Francesco Piepoli In X Susanna Price In X Giuseppe M C Rosano In X Frank Ruschitzka In X Anne Kathrine Skibelund In X In X
Abstract: Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online.
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Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease.

Open Access Issue 1 Vol 24 Published on 2022-01-01 PMID 34986851 PMCID PMC8734365
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Keywords: coronary artery disease, Cost-effectiveness, Cardiovascular Magnetic Resonance
DOI: https://doi.org/10.1186/s12968-021-00833-1
Authors: Ankur Pandya In X Yuan-Jui Yu In X Yin Ge In X Eike Nagel In X Raymond Y Kwong In X Rafidah Abu Bakar In X John D Grizzard In X Alexander E Merkler In X Ntobeko Ntusi In X Steffen E Petersen In X Nina Rashedi In X Juerg Schwitter In X Joseph B Selvanayagam In X James A White In X James Carr In X Subha V Raman In X Orlando P Simonetti In X Chiara Bucciarelli-Ducci In X Lilia M Sierra-Galan In X Victor A Ferrari In X Mona Bhatia In X Sebastian Kelle In X
Abstract:

Background

Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs.

Methods

We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography.

Results

CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model.

Conclusions

Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.
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Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.

Open Access Issue 7891 Vol 601 Published on 2022-01-01 PMID 34758478 PMCID PMC8732273
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Keywords:
DOI: https://doi.org/10.1038/s41586-021-04186-8
Authors: Leo Swadling In X Mariana O Diniz In X Nathalie M Schmidt In X Oliver E Amin In X Aneesh Chandran In X Emily Shaw In X Corinna Pade In X Joseph M Gibbons In X Nina Le Bert In X Anthony T Tan In X Anna Jeffery-Smith In X Cedric C S Tan In X Christine Y L Tham In X Stephanie Kucykowicz In X Gloryanne Aidoo-Micah In X Joshua Rosenheim In X Jessica Davies In X Marina Johnson In X Melanie P Jensen In X George Joy In X Laura E McCoy In X Ana M Valdes In X Benjamin M Chain In X David Goldblatt In X Daniel M Altmann In X Rosemary J Boyton In X Charlotte Manisty In X Thomas A Treibel In X James C Moon In X In X Lucy van Dorp In X Francois Balloux In X Áine McKnight In X Mahdad Noursadeghi In X Antonio Bertoletti In X Mala K Maini In X
Abstract: Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-3. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4-11), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication-transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae.
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Shape registration with learned deformations for 3D shape reconstruction from sparse and incomplete point clouds.

Issue N/A Vol 74 Published on 2021-12-01 PMID 34563860 PMCID N/A
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Keywords: Deep Learning, Graph Convolutional Network, Contours To Mesh Reconstruction, Cardiac Mesh Reconstruction, Cardiac Surface Reconstruction
DOI: https://doi.org/10.1016/j.media.2021.102228
Authors: Xiang Chen In X Nishant Ravikumar In X Yan Xia In X Rahman Attar In X Andres Diaz-Pinto In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: Shape reconstruction from sparse point clouds/images is a challenging and relevant task required for a variety of applications in computer vision and medical image analysis (e.g. surgical navigation, cardiac motion analysis, augmented/virtual reality systems). A subset of such methods, viz. 3D shape reconstruction from 2D contours, is especially relevant for computer-aided diagnosis and intervention applications involving meshes derived from multiple 2D image slices, views or projections. We propose a deep learning architecture, coined Mesh Reconstruction Network (MR-Net), which tackles this problem. MR-Net enables accurate 3D mesh reconstruction in real-time despite missing data and with sparse annotations. Using 3D cardiac shape reconstruction from 2D contours defined on short-axis cardiac magnetic resonance image slices as an exemplar, we demonstrate that our approach consistently outperforms state-of-the-art techniques for shape reconstruction from unstructured point clouds. Our approach can reconstruct 3D cardiac meshes to within 2.5-mm point-to-point error, concerning the ground-truth data (the original image spatial resolution is ∼1.8×1.8×10mm3). We further evaluate the robustness of the proposed approach to incomplete data, and contours estimated using an automatic segmentation algorithm. MR-Net is generic and could reconstruct shapes of other organs, making it compelling as a tool for various applications in medical image analysis.
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Medical image segmentation automatic quality control: A multi-dimensional approach.

Issue N/A Vol 74 Published on 2021-12-01 PMID 34455223 PMCID N/A
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Keywords: Deep Learning, Cmr Image Segmentation, Medical Image Segmentation Automatic Quality Control, Multi-dimensional Quality Control
DOI: https://doi.org/10.1016/j.media.2021.102213
Authors: Joris Fournel In X Axel Bartoli In X David Bendahan In X Maxime Guye In X Monique Bernard In X Elisa Rauseo In X Mohammed Y Khanji In X Steffen E Petersen In X Alexis Jacquier In X Badih Ghattas In X
Abstract: In clinical applications, using erroneous segmentations of medical images can have dramatic consequences. Current approaches dedicated to medical image segmentation automatic quality control do not predict segmentation quality at slice-level (2D), resulting in sub-optimal evaluations. Our 2D-based deep learning method simultaneously performs quality control at 2D-level and 3D-level for cardiovascular MR image segmentations. We compared it with 3D approaches by training both on 36,540 (2D) / 3842 (3D) samples to predict Dice Similarity Coefficients (DSC) for 4 different structures from the left ventricle, i.e., trabeculations (LVT), myocardium (LVM), papillary muscles (LVPM) and blood (LVC). The 2D-based method outperformed the 3D method. At the 2D-level, the mean absolute errors (MAEs) of the DSC predictions for 3823 samples, were 0.02, 0.02, 0.05 and 0.02 for LVM, LVC, LVT and LVPM, respectively. At the 3D-level, for 402 samples, the corresponding MAEs were 0.02, 0.01, 0.02 and 0.04. The method was validated in a clinical practice evaluation against semi-qualitative scores provided by expert cardiologists for 1016 subjects of the UK BioBank. Finally, we provided evidence that a multi-level QC could be used to enhance clinical measurements derived from image segmentations.
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Bright Is (Not Too) Bad: "Incidental" Nonischemic Fibrosis Associated With Good Outcomes in "Normal" Hearts.

Issue 12 Vol 14 Published on 2021-12-01 PMID 34274279 PMCID N/A
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Keywords: Myocarditis, Cardiovascular Magnetic Resonance, myocardial fibrosis, Late Gadolinium Enhancement, Sudden cardiac death
DOI: https://doi.org/10.1016/j.jcmg.2021.06.009
Authors: Steffen E Petersen In X Mohammed Y Khanji In X
Abstract: No Abstract Available
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Multi-Centre, Multi-Vendor and Multi-Disease Cardiac Segmentation: The M&Ms Challenge.

Issue 12 Vol 40 Published on 2021-12-01 PMID 34138702 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1109/tmi.2021.3090082
Authors: Victor M Campello In X Polyxeni Gkontra In X Cristian Izquierdo In X Carlos Martin-Isla In X Alireza Sojoudi In X Peter M Full In X Klaus Maier-Hein In X Yao Zhang In X Yao Zhang In X Zhiqiang He In X Jun Ma In X Mario Parreno In X Alberto Albiol In X Fanwei Kong In X Shawn C Shadden In X Jorge Corral Acero In X Vaanathi Sundaresan In X Mina Saber In X Mustafa Elattar In X Hongwei Li In X Bjoern Menze In X Firas Khader In X Christoph Haarburger In X Cian M Scannell In X Mitko Veta In X Adam Carscadden In X Kumaradevan Punithakumar In X Xiao Liu In X Sotirios A Tsaftaris In X Xiaoqiong Huang In X Xin Yang In X Lei Li In X Xiahai Zhuang In X David Vilades In X Martin L Descalzo In X Andrea Guala In X Lucia La Mura In X Matthias G Friedrich In X Ria Garg In X Julie Lebel In X Filipe Henriques In X Mahir Karakas In X Ersin Cavus In X Steffen E Petersen In X Sergio Escalera In X Santi Segui In X Jose F Rodriguez-Palomares In X Karim Lekadir In X
Abstract: The emergence of deep learning has considerably advanced the state-of-the-art in cardiac magnetic resonance (CMR) segmentation. Many techniques have been proposed over the last few years, bringing the accuracy of automated segmentation close to human performance. However, these models have been all too often trained and validated using cardiac imaging samples from single clinical centres or homogeneous imaging protocols. This has prevented the development and validation of models that are generalizable across different clinical centres, imaging conditions or scanner vendors. To promote further research and scientific benchmarking in the field of generalizable deep learning for cardiac segmentation, this paper presents the results of the Multi-Centre, Multi-Vendor and Multi-Disease Cardiac Segmentation (M&Ms) Challenge, which was recently organized as part of the MICCAI 2020 Conference. A total of 14 teams submitted different solutions to the problem, combining various baseline models, data augmentation strategies, and domain adaptation techniques. The obtained results indicate the importance of intensity-driven data augmentation, as well as the need for further research to improve generalizability towards unseen scanner vendors or new imaging protocols. Furthermore, we present a new resource of 375 heterogeneous CMR datasets acquired by using four different scanner vendors in six hospitals and three different countries (Spain, Canada and Germany), which we provide as open-access for the community to enable future research in the field.
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Maximal Wall Thickness Measurement in Hypertrophic Cardiomyopathy: Biomarker Variability and its Impact on Clinical Care.

Issue 11 Vol 14 Published on 2021-11-01 PMID 34147459 PMCID N/A
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Keywords: Echocardiography, hypertrophic cardiomyopathy, wall thickness, Cardiovascular Magnetic Resonance
DOI: https://doi.org/10.1016/j.jcmg.2021.03.032
Authors: Gabriella Captur In X Charlotte H Manisty In X Betty Raman In X Alberto Marchi In X Timothy C Wong In X Rina Ariga In X Anish Bhuva In X Elizabeth Ormondroyd In X Ilaria Lobascio In X Claudia Camaioni In X Savvas Loizos In X Jenade Bonsu-Ofori In X Aslan Turer In X Vlad G Zaha In X João B Augutsto In X Rhodri H Davies In X Andrew J Taylor In X Arthur Nasis In X Mouaz H Al-Mallah In X Sinitsyn Valentin In X Diego Perez de Arenaza In X Vimal Patel In X Mark Westwood In X Steffen E Petersen In X Chunming Li In X Lijun Tang In X Shiro Nakamori In X Reza Nezafat In X Raymond Y Kwong In X Carolyn Y Ho In X Alan G Fraser In X Hugh Watkins In X Perry M Elliott In X Stefan Neubauer In X Guy Lloyd In X Iacopo Olivotto In X Petros Nihoyannopoulos In X James C Moon In X
Abstract:

Objectives

The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).

Background

Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).

Methods

A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.

Results

MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).

Conclusions

Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.
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Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR.

Open Access Issue 11 Vol 14 Published on 2021-11-01 PMID 34023269 PMCID PMC8560640
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Keywords: Outcomes, Pulmonary Blood Volume, First Pass Perfusion
DOI: https://doi.org/10.1016/j.jcmg.2021.03.029
Authors: Andreas Seraphim In X Kristopher D Knott In X Katia Menacho In X Joao B Augusto In X Rhodri Davies In X Iain Pierce In X George Joy In X Anish N Bhuva In X Hui Xue In X Thomas A Treibel In X Jackie A Cooper In X Steffen E Petersen In X Marianna Fontana In X Alun D Hughes In X James C Moon In X Charlotte Manisty In X Peter Kellman In X
Abstract:

Objectives

The purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR.

Background

Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption.

Methods

In this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters.

Results

A total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002).

Conclusions

Pulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.
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Brain age estimation at tract group level and its association with daily life measures, cardiac risk factors and genetic variants.

Open Access Issue 1 Vol 11 Published on 2021-10-01 PMID 34663856 PMCID PMC8523533
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Keywords:
DOI: https://doi.org/10.1038/s41598-021-99153-8
Authors: Ahmed Salih In X Ilaria Boscolo Galazzo In X Zahra Raisi-Estabragh In X Elisa Rauseo In X Polyxeni Gkontra In X Steffen E Petersen In X Karim Lekadir In X André Altmann In X Petia Radeva In X Gloria Menegaz In X
Abstract: Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural ([Formula: see text]), Association ([Formula: see text]), and Projection ([Formula: see text]) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value [Formula: see text]) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes.
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The year 2020 in the European Heart Journal - Cardiovascular Imaging: part I.

Issue 11 Vol 22 Published on 2021-10-01 PMID 34463734 PMCID N/A
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Keywords: Echocardiography, Cardiovascular Magnetic Resonance, Nuclear Imaging,  Multimodality Imaging
DOI: https://doi.org/10.1093/ehjci/jeab148
Authors: Thor Edvardsen In X Erwan Donal In X Nina A Marsan In X Pál Maurovich-Horvat In X Marc R Dweck In X Gerald Maurer In X Steffen E Petersen In X Bernard Cosyns In X
Abstract: The European Heart Journal - Cardiovascular Imaging was launched in 2012 and has during these 9 years become one of the leading multimodality cardiovascular imaging journals. The journal is currently ranked as number 20 among all cardiovascular journals. Our journal is well established as one of the top cardiovascular journals and is the most important cardiovascular imaging journal in Europe. The most important studies published in our Journal in 2020 will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
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Diagnosing excessive trabeculation cardiomyopathy: in pursuit of the "holy grail".

Issue 10 Vol 31 Published on 2021-10-01 PMID 34331115 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1007/s00330-021-08207-y
Authors: Fabrizio Ricci In X Mohammed Y Khanji In X Steffen E Petersen In X
Abstract: No Abstract Available
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Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study.

Open Access Issue 10 Vol 2 Published on 2021-10-01 PMID 34250515 PMCID PMC8260104
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Keywords:
DOI: https://doi.org/10.1016/s2666-5247(21)00146-4
Authors: Rishi K Gupta In X Joshua Rosenheim In X Lucy C Bell In X Aneesh Chandran In X Jose A Guerra-Assuncao In X Gabriele Pollara In X Matthew Whelan In X Jessica Artico In X George Joy In X Hibba Kurdi In X Daniel M Altmann In X Rosemary J Boyton In X Mala K Maini In X Aine McKnight In X Jonathan Lambourne In X Teresa Cutino-Moguel In X Charlotte Manisty In X Thomas A Treibel In X James C Moon In X Benjamin M Chain In X Mahdad Noursadeghi In X In X
Abstract:

Background

We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.

Methods

We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for "viral infection", "transcriptome", "biomarker", and "blood". We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.

Findings

We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27-47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91-0·99), sensitivity 0·84 (0·70-0·93), and specificity 0·95 (0·85-0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91-0·95).

Interpretation

Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge.

Funding

Barts Charity, Wellcome Trust, and National Institute of Health Research.
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Genome-wide association study of cardiac troponin I in the general population.

Open Access Issue 21 Vol 30 Published on 2021-10-01 PMID 33961016 PMCID PMC8522636
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Keywords:
DOI: https://doi.org/10.1093/hmg/ddab124
Authors: Marta R Moksnes In X Helge Røsjø In X Anne Richmond In X Magnus N Lyngbakken In X Sarah E Graham In X Ailin Falkmo Hansen In X Brooke N Wolford In X Sarah A Gagliano Taliun In X Jonathon LeFaive In X Humaira Rasheed In X Laurent F Thomas In X Wei Zhou In X Nay Aung In X Ida Surakka In X Nicholas J Douville In X Archie Campbell In X David J Porteous In X Steffen E Petersen In X Patricia B Munroe In X Paul Welsh In X Naveed Sattar In X George Davey Smith In X Lars G Fritsche In X Jonas B Nielsen In X Bjørn Olav Åsvold In X Kristian Hveem In X Caroline Hayward In X Cristen J Willer In X Ben M Brumpton In X Torbjørn Omland In X
Abstract: Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes are unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study, and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further use two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction (AMI) and heart failure (HF). We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1688 phecodes and 83 continuous traits in UK Biobank showed associations between a genetic risk score for cTnI and cardiac arrhythmias, metabolic and anthropometric measures. Using two-sample Mendelian randomization, we confirmed the non-causal role of cTnI in AMI (5948 cases, 355 246 controls). We found indications for a causal role of cTnI in HF (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals). Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for AMI in the general population. Using genetically informed methods for causal inference helps inform the role and value of measuring cTnI in the general population.
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2021 ESC Guidelines on cardiovascular disease prevention in clinical practice.

Issue 34 Vol 42 Published on 2021-09-01 PMID 34458905 PMCID N/A
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Keywords: Population, Lipids, Air pollution, Climate change, Blood pressure, Nutrition, Diabetes, Prevention, Smoking, Psychosocial factors, risk management, Guidelines, Risk Estimation, Shared Decision-making, Healthy Lifestyle, Lifetime Risk, Personalized, Stepwise Approach, Lifetime Benefit
DOI: https://doi.org/10.1093/eurheartj/ehab484
Authors: Frank L J Visseren In X François Mach In X Yvo M Smulders In X David Carballo In X Konstantinos C Koskinas In X Maria Bäck In X Athanase Benetos In X Alessandro Biffi In X José-Manuel Boavida In X Davide Capodanno In X Bernard Cosyns In X Carolyn Crawford In X Constantinos H Davos In X Ileana Desormais In X Emanuele Di Angelantonio In X Oscar H Franco In X Sigrun Halvorsen In X F D Richard Hobbs In X Monika Hollander In X Ewa A Jankowska In X Matthias Michal In X Simona Sacco In X Naveed Sattar In X Lale Tokgozoglu In X Serena Tonstad In X Konstantinos P Tsioufis In X Ineke van Dis In X Isabelle C van Gelder In X Christoph Wanner In X Bryan Williams In X In X In X
Abstract: No Abstract Available
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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

Issue 36 Vol 42 Published on 2021-09-01 PMID 34447992 PMCID N/A
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Keywords: Transplantation, Diagnosis, Natriuretic peptides, Arrhythmias, Ejection fraction, Heart Failure, Hospitalization, Guidelines, Mechanical Circulatory Support, Pharmacotherapy, Acute Heart Failure, Multidisciplinary Management, Cardiac Resynchronization Therapy, Comorbidities, Advanced Heart Failure, Neuro-hormonal Antagonists
DOI: https://doi.org/10.1093/eurheartj/ehab368
Authors: Theresa A McDonagh In X Marco Metra In X Marianna Adamo In X Roy S Gardner In X Andreas Baumbach In X Michael Böhm In X Haran Burri In X Javed Butler In X Jelena Čelutkienė In X Ovidiu Chioncel In X John G F Cleland In X Andrew J S Coats In X Maria G Crespo-Leiro In X Dimitrios Farmakis In X Martine Gilard In X Stephane Heymans In X Arno W Hoes In X Tiny Jaarsma In X Ewa A Jankowska In X Mitja Lainscak In X Carolyn S P Lam In X Alexander R Lyon In X John J V McMurray In X Alexandre Mebazaa In X Richard Mindham In X Claudio Muneretto In X Massimo Francesco Piepoli In X Susanna Price In X Giuseppe M C Rosano In X Frank Ruschitzka In X Anne Kathrine Skibelund In X In X
Abstract: No Abstract Available
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One-step anatomic and function testing by cardiac CT versus second-line functional testing in symptomatic patients with coronary artery stenosis: head-to-head comparison of CT-derived fractional flow reserve and myocardial perfusion imaging.

Issue 7 Vol 17 Published on 2021-09-01 PMID 33196446 PMCID PMC9724926
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Keywords:
DOI: https://doi.org/10.4244/eij-d-20-00905
Authors: Jelmer Westra In X Zehang Li In X Laust Dupont Rasmussen In X Simon Winther In X Guanyu Li In X Louise Nissen In X Steffen E Petersen In X June Anita Ejlersen In X Christin Isaksen In X Lars Christian Gormsen In X Grazina Urbonaviciene In X Ashkan Eftekhari In X Tingwen Weng In X Xinkai Qu In X Hans Erik Bøtker In X Evald Høj Christiansen In X Niels Ramsing Holm In X Morten Bøttcher In X Shengxian Tu In X
Abstract:

Background

CT-QFR is a novel coronary computed tomography angiography (CTA)-based method for on-site evaluation of patients with suspected obstructive coronary artery disease (CAD).

Aims

We aimed to compare the diagnostic performance of CT-QFR with myocardial perfusion scintigraphy (MPS) and cardiovascular magnetic resonance (CMR) as second-line tests in patients with suspected obstructive CAD after coronary CTA.

Methods

A paired analysis of CT-QFR and MPS or CMR, with an invasive FFR-based classification as reference standard was carried out. Symptomatic patients with >50% diameter stenosis on coronary CTA were randomised to MPS or CMR and referred for invasive coronary angiography.

Results

The rate of coronary CTA not feasible for CT-QFR analysis was 17%. Paired patient-level data were available for 118 patients in the MPS group and 113 in the CMR group. Patient-level diagnostic accuracy was better for CT-QFR than for both MPS (82.2% [95% CI: 75.2-89.2] vs 70.3% [95% CI: 62.0-78.7], p=0.029) and CMR (77.0% [95% CI: 69.1-84.9] vs 65.5% [95% CI: 56.6-74.4], p=0.047). Following a positive coronary CTA and with the intention to diagnose, CT-QFR, CMR and MPS were equally suitable as rule-in and rule-out modalities.

Conclusions

The diagnostic performance of CT-QFR as a second-line test was at least similar to MPS and CMR for the evaluation of obstructive CAD in symptomatic patients presenting with ≥50% diameter stenosis on coronary CTA.
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Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.

Open Access Issue N/A Vol 70 Published on 2021-08-01 PMID 34304048 PMCID PMC8299112
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Keywords:
DOI: https://doi.org/10.1016/j.ebiom.2021.103485
Authors: Qingning Wang In X Veryan Codd In X Zahra Raisi-Estabragh In X Crispin Musicha In X Vasiliki Bountziouka In X Stephen Kaptoge In X Elias Allara In X Emanuele Di Angelantonio In X Adam S Butterworth In X Angela M Wood In X John R Thompson In X Steffen E Petersen In X Nicholas C Harvey In X John N Danesh In X Nilesh J Samani In X Christopher P Nelson In X
Abstract: Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.
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Probabilistic mapping of human functional brain networks identifies regions of high group consensus.

Open Access Issue N/A Vol 237 Published on 2021-08-01 PMID 34000397 PMCID PMC8296467
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Keywords: fMRI, Networks, Individual Differences, Functional Connectivity
DOI: https://doi.org/10.1016/j.neuroimage.2021.118164
Authors: Ally Dworetsky In X Benjamin A Seitzman In X Babatunde Adeyemo In X Maital Neta In X Rebecca S Coalson In X Steven E Petersen In X Caterina Gratton In X
Abstract: Many recent developments surrounding the functional network organization of the human brain have focused on data that have been averaged across groups of individuals. While such group-level approaches have shed considerable light on the brain's large-scale distributed systems, they conceal individual differences in network organization, which recent work has demonstrated to be common and widespread. This individual variability produces noise in group analyses, which may average together regions that are part of different functional systems across participants, limiting interpretability. However, cost and feasibility constraints may limit the possibility for individual-level mapping within studies. Here our goal was to leverage information about individual-level brain organization to probabilistically map common functional systems and identify locations of high inter-subject consensus for use in group analyses. We probabilistically mapped 14 functional networks in multiple datasets with relatively high amounts of data. All networks show "core" (high-probability) regions, but differ from one another in the extent of their higher-variability components. These patterns replicate well across four datasets with different participants and scanning parameters. We produced a set of high-probability regions of interest (ROIs) from these probabilistic maps; these and the probabilistic maps are made publicly available, together with a tool for querying the network membership probabilities associated with any given cortical location. These quantitative estimates and public tools may allow researchers to apply information about inter-subject consensus to their own fMRI studies, improving inferences about systems and their functional specializations.
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Sex-specific associations between alcohol consumption, cardiac morphology, and function as assessed by magnetic resonance imaging: insights form the UK Biobank Population Study.

Issue 9 Vol 22 Published on 2021-08-01 PMID 33313691 PMCID PMC7613253
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Keywords: alcohol consumption, Magnetic Resonance Imaging, Uk Biobank, Cardiac Morphology And Structure
DOI: https://doi.org/10.1093/ehjci/jeaa242
Authors: Judit Simon In X Kenneth Fung In X Márton Kolossváry In X Mihir M Sanghvi In X Nay Aung In X Jose Miguel Paiva In X Elena Lukaschuk In X Valentina Carapella In X Béla Merkely In X Marcio S Bittencourt In X Júlia Karády In X Aaron M Lee In X Stefan K Piechnik In X Stefan Neubauer In X Pál Maurovich-Horvat In X Steffen E Petersen In X
Abstract:

Aims

Data regarding the effects of regular alcohol consumption on cardiac anatomy and function are scarce. Therefore, we sought to determine the relationship between regular alcohol intake and cardiac structure and function as evaluated with cardiac magnetic resonance imaging.

Methods and results

Participants of the UK Biobank who underwent cardiac magnetic resonance were enrolled in our analysis. Data regarding regular alcohol consumption were obtained from questionnaires filled in by the study participants. Exclusion criteria were poor image quality, missing, or incongruent data regarding alcohol drinking habits, prior drinking, presence of heart failure or angina, and prior myocardial infarction or stroke. Overall, 4335 participants (61.5 ± 7.5 years, 47.6% male) were analysed. We used multivariate linear regression models adjusted for age, ethnicity, body mass index, smoking, hypertension, diabetes mellitus, physical activity, cholesterol level, and Townsend deprivation index to examine the relationship between regular alcohol intake and cardiac structure and function. In men, alcohol intake was independently associated with marginally increased left ventricular end-diastolic volume [β = 0.14; 95% confidence interval (CI) = 0.05-0.24; P = 0.004], left ventricular stroke volume (β = 0.08; 95% CI = 0.03-0.14; P = 0.005), and right ventricular stroke volume (β = 0.08; 95% CI = 0.02-0.13; P = 0.006). In women, alcohol consumption was associated with increased left atrium volume (β = 0.14; 95% CI = 0.04-0.23; P = 0.006).

Conclusion

Alcohol consumption is independently associated with a marginal increase in left and right ventricular volumes in men, but not in women, whereas alcohol intake showed an association with increased left atrium volume in women. Our results suggest that there is only minimal relationship between regular alcohol consumption and cardiac morphology and function in an asymptomatic middle-aged population.
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Vitamin D and coronavirus disease 2019 (COVID-19): rapid evidence review.

Open Access Issue 7 Vol 33 Published on 2021-07-01 PMID 34118024 PMCID PMC8195723
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Keywords: Vitamin D, Osteoporosis, Vitamin D deficiency, respiratory infection, Musculoskeletal Health, Coronavirus Disease 2019 (Covid-19), Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-cov-2)
DOI: https://doi.org/10.1007/s40520-021-01894-z
Authors: Zahra Raisi-Estabragh In X Adrian R Martineau In X Elizabeth M Curtis In X Rebecca J Moon In X Andrea Darling In X Susan Lanham-New In X Kate A Ward In X Cyrus Cooper In X Patricia B Munroe In X Steffen E Petersen In X Nicholas C Harvey In X
Abstract:

Background

The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has re-ignited interest in the possible role of vitamin D in modulation of host responses to respiratory pathogens. Indeed, vitamin D supplementation has been proposed as a potential preventative or therapeutic strategy. Recommendations for any intervention, particularly in the context of a potentially fatal pandemic infection, should be strictly based on clinically informed appraisal of the evidence base. In this narrative review, we examine current evidence relating to vitamin D and COVID-19 and consider the most appropriate practical recommendations.

Observations

Although there are a growing number of studies investigating the links between vitamin D and COVID-19, they are mostly small and observational with high risk of bias, residual confounding, and reverse causality. Extrapolation of molecular actions of 1,25(OH)2-vitamin D to an effect of increased 25(OH)-vitamin D as a result of vitamin D supplementation is generally unfounded, as is the automatic conclusion of causal mechanisms from observational studies linking low 25(OH)-vitamin D to incident disease. Efficacy is ideally demonstrated in the context of adequately powered randomised intervention studies, although such approaches may not always be feasible.

Conclusions

At present, evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. In the absence of any further compelling data, adherence to existing national guidance on vitamin D supplementation to prevent vitamin D deficiency, predicated principally on maintaining musculoskeletal health, appears appropriate.
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Super-Resolution of Cardiac MR Cine Imaging using Conditional GANs and Unsupervised Transfer Learning.

Issue N/A Vol 71 Published on 2021-07-01 PMID 33910110 PMCID N/A
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Keywords: Optical Flow, Cardiac Mri, Super-resolution, Deep Learning, Conditional Batch Normalisation, Conditional Generative Adversarial Net
DOI: https://doi.org/10.1016/j.media.2021.102037
Authors: Yan Xia In X Nishant Ravikumar In X John P Greenwood In X Stefan Neubauer In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: High-resolution (HR), isotropic cardiac Magnetic Resonance (MR) cine imaging is challenging since it requires long acquisition and patient breath-hold times. Instead, 2D balanced steady-state free precession (SSFP) sequence is widely used in clinical routine. However, it produces highly-anisotropic image stacks, with large through-plane spacing that can hinder subsequent image analysis. To resolve this, we propose a novel, robust adversarial learning super-resolution (SR) algorithm based on conditional generative adversarial nets (GANs), that incorporates a state-of-the-art optical flow component to generate an auxiliary image to guide image synthesis. The approach is designed for real-world clinical scenarios and requires neither multiple low-resolution (LR) scans with multiple views, nor the corresponding HR scans, and is trained in an end-to-end unsupervised transfer learning fashion. The designed framework effectively incorporates visual properties and relevant structures of input images and can synthesise 3D isotropic, anatomically plausible cardiac MR images, consistent with the acquired slices. Experimental results show that the proposed SR method outperforms several state-of-the-art methods both qualitatively and quantitatively. We show that subsequent image analyses including ventricle segmentation, cardiac quantification, and non-rigid registration can benefit from the super-resolved, isotropic cardiac MR images, to produce more accurate quantitative results, without increasing the acquisition time. The average Dice similarity coefficient (DSC) for the left ventricular (LV) cavity and myocardium are 0.95 and 0.81, respectively, between real and synthesised slice segmentation. For non-rigid registration and motion tracking through the cardiac cycle, the proposed method improves the average DSC from 0.75 to 0.86, compared to the original resolution images.
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Prevalence of Hypertrophic Cardiomyopathy in the UK Biobank Population.

Open Access Issue 7 Vol 6 Published on 2021-07-01 PMID 33851951 PMCID PMC8047757
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Keywords:
DOI: https://doi.org/10.1001/jamacardio.2021.0689
Authors: Luis R Lopes In X Nay Aung In X Stefan van Duijvenboden In X Patricia B Munroe In X Perry M Elliott In X Steffen E Petersen In X
Abstract: No Abstract Available
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Automated myocardial segmentation in native t1-mapping cardiovascular magnetic resonance images based on machine learning: a validation study in the UK biobank"s covid-19 subset

Open Access Issue Suppl 2 Vol 22 Published on 2021-06-01 PMID N/A PMCID PMC8344639
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Keywords:
DOI: #
Authors: E Rauseo In X L Lockhart In X JM Paiva In X K Fung In X MY Khanji In X Z Raisi-Estabragh In X A Amir-Khalili In X SE Petersen In X
Abstract: Abstract

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Innovate UK

Background

 Regional assessment of septal native T1 values with cardiovascular magnetic resonance (CMR) is used to characterise diffuse myocardial diseases. Previous studies suggest its potential role in detecting early pathological alterations, which may help identify high-risk subjects at early disease stages. Automated analysis of myocardial native T1 images may enable faster CMR analysis and reduce inter-observer variability of manual analysis. However, the technical performance of such methodologies has not been previously reported.

Purpose

 We tested, in a subset of UK Biobank participants, the degree of agreement between CMR septal myocardial T1 values obtained from our machine learning (ML) algorithm and septal native T1 values computed from manual segmentations.

Methods

 We analysed the first 292 participants who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and had CMR imaging (1.5 Tesla, Siemens MAGNETOM Aera). T1 mapping was performed in a single mid-ventricular short axis (SAX) slice using ShMOLLI (WIP780B) sequences. Three experienced CMR readers independently measured native T1 values by manually placing a single region of interest (ROI) covering half of the anteroseptal and half of the inferoseptal wall using cvi42 post-processing software (version 5.11). A mean T1 value for each participant was then calculated. A ML algorithm developed by Circle Cardiovascular Imaging Inc. was then applied to the same images to derive the myocardium T1 values automatically. The algorithm was previously trained to segment myocardium from SAX T1 and non-T1 mapping images on two external CMR datasets. We compared the mean septal ROI T1 values to the mean myocardium T1 values predicted by the ML algorithm.

Results

 Two studies were excluded after quality control. The ML-derived and the manually calculated mean T1 values were significantly correlated (r = 0.82, p < 0.001). The Bland-Altman analysis between the two methods showed a mean bias of 3.64 ms, with 95% limits of agreement of −38.88 to 53.46 ms, indicating good agreement (figure 1).

Conclusions

 We demonstrated strong correlation and good agreement between native T1 values obtained from our automated analysis method and manual T1 septal analysis in a subset of UK Biobank participants. This algorithm may represent a valuable tool for clinicians allowing for fast and potentially less operator-dependent myocardial tissue characterisation. However, validation of more extensive datasets and quality control processes are needed. Abstract Figure 1: Bland-Altman plot.
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Lifelong learning as a clinical academic key to job satisfaction.

Issue 11 Vol 107 Published on 2021-06-01 PMID 33127649 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1136/heartjnl-2020-318317
Authors: Steffen Erhard Petersen In X
Abstract: No Abstract Available
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Subclinical Changes in Cardiac Functional Parameters as Determined by Cardiovascular Magnetic Resonance (CMR) Imaging in Sleep Apnea and Snoring: Findings from UK Biobank.

Open Access Issue 6 Vol 57 Published on 2021-05-01 PMID 34072775 PMCID PMC8230102
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Keywords: Heart, epidemiology, Sleep Apnea, Cardiac Mri
DOI: https://doi.org/10.3390/medicina57060555
Authors: Adrian Curta In X Holger Hetterich In X Regina Schinner In X Aaron M Lee In X Wieland Sommer In X Nay Aung In X Mihir M Sanghvi In X Kenneth Fung In X Elena Lukaschuk In X Jackie A Cooper In X José Miguel Paiva In X Valentina Carapella In X Stefan Neubauer In X Stefan K Piechnik In X Steffen E Petersen In X
Abstract: Background and Objectives: Obstructive sleep apnea (OSA) is a common disorder with an increased risk for left ventricular and right ventricular dysfunction. Most studies to date have examined populations with manifest cardiovascular disease using echocardiography to analyze ventricular dysfunction with little or no reference to ventricular volumes or myocardial mass. Our aim was to explore these parameters with cardiac MRI. We hypothesized that there would be stepwise increase in left ventricular mass and right ventricular volumes from the unaffected, to the snoring and the OSA group. Materials and Methods: We analyzed cardiac MRI data from 4978 UK Biobank participants free from cardiovascular disease. Participants were allocated into three cohorts: with OSA, with self-reported snoring and without OSA or snoring (n = 118, 1886 and 2477). We analyzed cardiac parameters from balanced cine-SSFP sequences and indexed them to body surface area. Results: Patients with OSA were mostly males (47.3% vs. 79.7%; p < 0.001) with higher body mass index (25.7 ± 4.0 vs. 31.3 ± 5.3 kg/m²; p < 0.001) and higher blood pressure (135 ± 18 vs. 140 ± 17 mmHg; p = 0.012) compared to individuals without OSA or snoring. Regression analysis showed a significant effect for OSA in left ventricular end-diastolic index (LVEDVI) (β = -4.9 ± 2.4 mL/m²; p = 0.040) and right ventricular end-diastolic index (RVEDVI) (β = -6.2 ± 2.6 mL/m²; p = 0.016) in females and for right ventricular ejection fraction (RVEF) (β = 1.7 ± 0.8%; p = 0.031) in males. A significant effect was discovered in snoring females for left ventricular mass index (LVMI) (β = 3.5 ± 0.9 g/m²; p < 0.001) and in males for left ventricular ejection fraction (LVEF) (β = 1.0 ± 0.3%; p = 0.001) and RVEF (β = 1.2 ± 0.3%; p < 0.001). Conclusion: Our study suggests that OSA is highly underdiagnosed and that it is an evolving process with gender specific progression. Females with OSA show significantly lower ventricular volumes while males with snoring show increased ejection fractions which may be an early sign of hypertrophy. Separate prospective studies are needed to further explore the direction of causality.
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Anatomically robust proton therapy using multiple planning computed tomography scans for locally advanced prostate cancer.

Issue 5 Vol 60 Published on 2021-05-01 PMID 33646069 PMCID N/A
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Keywords: prostate cancer, Treatment Planning, Anatomical Robust Proton Therapy, Multiple Cts, Patient-specific Targets
DOI: https://doi.org/10.1080/0284186x.2021.1892181
Authors: Kia Busch In X Benjamin Dahl In X Stine E Petersen In X Heidi S Rønde In X Lise Bentzen In X Sara Pilskog In X Ludvig P Muren In X
Abstract:

Background

Proton therapy (PT) is sensitive towards anatomical changes that may occur during a treatment course. The aim of this study was to investigate if anatomically robust PT (ARPT) plans incorporating patient-specific target motion improved target coverage while still sparing normal tissues, when applied on locally advanced prostate cancer patients where pelvic irradiation is indicated.

Material and methods

A planning computed tomography (CT) scan used for dose calculation and two additional CTs (acquired on different days) were used to make patient-specific targets for the ARPT plans on the eight included patients. The plans were compared to a conventional robust PT plan and a volumetric modulated arc therapy (VMAT) photon plan, which were derived from the planning CT (pCT). Worst-case robust optimisation was used for all proton plans with a setup uncertainty of 5 mm and a range uncertainty of 3.5%. Target coverage (V95% and D95%) and normal tissue doses (V5-75 Gy) were evaluated on 6-8 rCTs per patient.

Results

The ARPT plans improved the prostate target coverage for the most challenging patient compared to conventional robust PT plans (20% point increase for V95% and 31 Gy increase for D95%). Across the whole cohort the estimated mean value for V95% was 97% for the ARPT plans and 95% for the conventional robust PT plans. The ARPT plans had a slight, statistically insignificant increase in normal tissue doses compared to the conventional robust proton plans. Compared to VMAT, the ARPT plans significantly reduced the normal tissue doses in the low-to-intermediate dose range.

Conclusions

While both proton plans reduced the low-to-intermediate normal tissue doses compared to VMAT, ARPT plans improved the target coverage for the most challenging patient without significantly increasing the normal tissue doses compared to conventional robust PT plans.
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Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose.

Open Access Issue N/A Vol N/A Published on 2021-04-01 PMID 33931567 PMCID PMC8168614
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Keywords:
DOI: https://doi.org/10.1126/science.abh1282
Authors: Catherine J Reynolds In X Corinna Pade In X Joseph M Gibbons In X David K Butler In X Ashley D Otter In X Katia Menacho In X Marianna Fontana In X Angelique Smit In X Jane E Sackville-West In X Teresa Cutino-Moguel In X Mala K Maini In X Benjamin Chain In X Mahdad Noursadeghi In X In X Tim Brooks In X Amanda Semper In X Charlotte Manisty In X Thomas A Treibel In X James C Moon In X In X Ana M Valdes In X Áine McKnight In X Daniel M Altmann In X Rosemary Boyton In X
Abstract: SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.
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Brain network reorganisation in an adolescent after bilateral perinatal strokes.

Issue 4 Vol 20 Published on 2021-04-01 PMID 33743230 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/s1474-4422(21)00062-4
Authors: Timothy O Laumann In X Mario Ortega In X Catherine R Hoyt In X Nicole A Seider In X Abraham Z Snyder In X Nico Uf Dosenbach In X In X
Abstract: No Abstract Available
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Adverse cardiovascular magnetic resonance phenotypes are associated with greater likelihood of incident coronavirus disease 2019: findings from the UK Biobank.

Open Access Issue 4 Vol 33 Published on 2021-04-01 PMID 33683678 PMCID PMC7938275
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Keywords: Cardiovascular Magnetic Resonance, Coronavirus Disease 2019 (Covid-19), Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-cov-2)
DOI: https://doi.org/10.1007/s40520-021-01808-z
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Jackie Cooper In X Kenneth Fung In X José M Paiva In X Mohammed Y Khanji In X Elisa Rauseo In X Luca Biasiolli In X Betty Raman In X Stefan K Piechnik In X Stefan Neubauer In X Patricia B Munroe In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Background

Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes.

Aims

We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19.

Methods

We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction.

Results

We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity.

Discussion

We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors.

Conclusions

Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.
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Network variants are similar between task and rest states.

Open Access Issue N/A Vol 229 Published on 2021-04-01 PMID 33454409 PMCID PMC8080895
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Keywords:
DOI: https://doi.org/10.1016/j.neuroimage.2021.117743
Authors: Brian T Kraus In X Diana Perez In X Zach Ladwig In X Benjamin A Seitzman In X Ally Dworetsky In X Steven E Petersen In X Caterina Gratton In X
Abstract: Recent work has demonstrated that individual-specific variations in functional networks (termed "network variants") can be identified in individuals using resting state functional magnetic resonance imaging (fMRI). These network variants exhibit reliability over time, suggesting that they may be trait-like markers of individual differences in brain organization. However, while networks variants are reliable at rest, is is still untested whether they are stable between task and rest states. Here, we use precision data from the Midnight Scan Club (MSC) to demonstrate that (1) task data can be used to identify network variants reliably, (2) these network variants show substantial spatial overlap with those observed in rest, although state-specific effects are present, (3) network variants assign to similar canonical functional networks in task and rest states, and (4) single tasks or a combination of multiple tasks produce similar network variants to rest. Together, these findings further reinforce the trait-like nature of network variants and demonstrate the utility of using task data to define network variants.
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Cardiology training using technology.

Open Access Issue 15 Vol 42 Published on 2021-04-01 PMID 33370432 PMCID PMC7799125
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Keywords:
DOI: https://doi.org/10.1093/eurheartj/ehaa1030
Authors: Jun Hua Chong In X Fabrizio Ricci In X Steffen E Petersen In X Mohammed Y Khanji In X
Abstract: No Abstract Available
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Attention Alterations in Pediatric Anxiety: Evidence From Behavior and Neuroimaging.

Issue 7 Vol 89 Published on 2021-04-01 PMID 33012520 PMCID PMC9166685
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Keywords: Attention, fMRI, Inferior Frontal Gyrus, Pediatric Anxiety, Network Neuroscience, Ventral Attention
DOI: https://doi.org/10.1016/j.biopsych.2020.07.016
Authors: Michael T Perino In X Qiongru Yu In X Michael J Myers In X Jennifer C Harper In X William T Baumel In X Steven E Petersen In X Deanna M Barch In X Joan L Luby In X Chad M Sylvester In X
Abstract:

Background

Pediatric anxiety disorders involve greater capture of attention by threatening stimuli. However, it is not known if disturbances extend to nonthreatening stimuli, as part of a pervasive disturbance in attention-related brain systems. We hypothesized that pediatric anxiety involves greater capture of attention by salient, nonemotional stimuli, coupled with greater activity in the portion of the inferior frontal gyrus (IFG) specific to the ventral attention network (VAN).

Methods

A sample of children (n = 129, 75 girls, mean 10.6 years of age), approximately half of whom met criteria for a current anxiety disorder, completed a task measuring involuntary capture of attention by nonemotional (square boxes) and emotional (angry and neutral faces) stimuli. A subset (n = 61) completed a task variant during functional magnetic resonance imaging. A priori analyses examined activity in functional brain areas within the right IFG, supplemented by a whole-brain, exploratory analysis.

Results

Higher clinician-rated anxiety was associated with greater capture of attention by nonemotional, salient stimuli (F1,125 = 4.94, p = .028) and greater activity in the portion of the IFG specific to the VAN (F1,57 = 10.311, p = .002). Whole-brain analyses confirmed that the effect of anxiety during capture of attention was most pronounced in the VAN portion of the IFG, along with additional areas of the VAN and the default mode network.

Conclusions

The pathophysiology of pediatric anxiety appears to involve greater capture of attention to salient stimuli, as well as greater activity in attention-related brain networks. These results provide novel behavioral and brain-based targets for treatment of pediatric anxiety disorders.
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Human kidney graft survival correlates with structural parameters in baseline biopsies: a quantitative observational cohort study with more than 14 years' follow-up.

Issue 4 Vol 478 Published on 2021-04-01 PMID 32986179 PMCID N/A
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Keywords: Morphometry, Quantification, Cohort study, Structural parameters, stereology, Long Term, Prospective, Baseline Biopsy, Human Kidney Graft
DOI: https://doi.org/10.1007/s00428-020-02924-3
Authors: Anne R Ellingsen In X Kaj A Jørgensen In X Ruth Østerby In X Steffen E Petersen In X Svend Juul In X Niels Marcussen In X Jens R Nyengaard In X
Abstract: This prospective cohort study evaluates associations between structural and ultrastructural parameters in baseline biopsies from human kidney transplants and long-term graft survival after more than 14 years' follow-up. Baseline kidney graft biopsies were obtained prospectively from 54 consecutive patients receiving a kidney transplant at a single institution. Quantitative measurements were performed on the baseline biopsies by computer-assisted light microscopy and electron microscopy. Stereology-based techniques estimated the fraction of interstitial tissue, the volume of glomeruli, mesangial fraction, and basement membrane thickness of glomerular capillaries. The fraction of occluded glomeruli and scores according to the Banff classification were achieved. Kidney graft survival was analyzed by Kaplan-Meier estimates and Cox regression. Association to long-term kidney function was also analyzed. The long-term surviving kidney transplants were characterized at implantation by less arteriolar hyaline thickening (P < 0.001) and less interstitial fibrosis (P = 0.001), as well as a lower fraction of occluded glomeruli (P = 0.004) and lower glomerular volume (P = 0.03). At the latest follow-up, eGFR was decreased by 12 ml/min/1.73 m2 per unit increase in the score for arteriolar hyalinosis at implantation (P = 0.02), and eGFR was decreased by 19 ml/min/1.73 m2 per 106 μm3 increase in glomerular volume at baseline (P = 0.03). The unbiased Cavalieri estimate of glomerular volume and the ultrastructural parameters are the first to be evaluated in a cohort study with prospective follow-up for more than 14 years. The study shows that baseline biopsies from human kidney grafts contain extraordinary long-term prognostic information, and it highlights the importance of these intrinsic graft factors.
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2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.

Issue 14 Vol 42 Published on 2021-04-01 PMID 32860058 PMCID N/A
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Keywords: Nitrates, Heparin, Myocardial infarction, Diabetes, Anticoagulation, Angioplasty, Stent, Unstable angina, Revascularization, antiplatelet, Enoxaparin, acute coronary syndrome, aspirin, Recommendations, Guidelines, European Society Of Cardiology, Clopidogrel, Bypass Surgery, Platelet Inhibition, Myocardial Ischaemia, Betablockers, Fondaparinux, Triple Therapy, Glycoprotein Iib/iiia Inhibitors, Bivalirudin, Ticagrelor, Prasugrel, Rivaroxaban, Atherothrombosis, Apixaban, Dabigatran, Non-st-elevation Myocardial Infarction, Chest Pain Unit, Edoxaban, Early Invasive Strategy, Bleedings, Cangrelor, High-sensitivity Troponin, Acute Cardiac Care, Rhythm Monitoring, Minoca, Dual Antithrombotic Therapy
DOI: https://doi.org/10.1093/eurheartj/ehaa575
Authors: Jean-Philippe Collet In X Holger Thiele In X Emanuele Barbato In X Olivier Barthélémy In X Johann Bauersachs In X Deepak L Bhatt In X Paul Dendale In X Maria Dorobantu In X Thor Edvardsen In X Thierry Folliguet In X Chris P Gale In X Martine Gilard In X Alexander Jobs In X Peter Jüni In X Ekaterini Lambrinou In X Basil S Lewis In X Julinda Mehilli In X Emanuele Meliga In X Béla Merkely In X Christian Mueller In X Marco Roffi In X Frans H Rutten In X Dirk Sibbing In X George C M Siontis In X In X
Abstract: No Abstract Available
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Variation in left ventricular cardiac magnetic resonance normal reference ranges: systematic review and meta-analysis.

Open Access Issue 5 Vol 22 Published on 2021-04-01 PMID 32460308 PMCID PMC8081427
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Keywords: Left ventricle, Cardiac Magnetic Resonance, Reference Range, Normal Range
DOI: https://doi.org/10.1093/ehjci/jeaa089
Authors: Zahra Raisi-Estabragh In X Asmaa A M Kenawy In X Nay Aung In X Jackie Cooper In X Patricia B Munroe In X Nicholas C Harvey In X Steffen E Petersen In X Mohammed Y Khanji In X
Abstract:

Aims

To determine population-related and technical sources of variation in cardiac magnetic resonance (CMR) reference ranges for left ventricular (LV) quantification through a formal systematic review and meta-analysis.

Methods and results

This study is registered with the International Prospective Register of Systematic Reviews (CRD42019147161). Relevant studies were identified through electronic searches and assessed by two independent reviewers based on predefined criteria. Fifteen studies comprising 2132 women and 1890 men aged 20-91 years are included in the analysis. Pooled LV reference ranges calculated using random effects meta-analysis with inverse variance weighting revealed significant differences by age, sex, and ethnicity. Men had larger LV volumes and higher LV mass than women [LV end-diastolic volume (mean difference = 6.1 mL/m2, P-value = 0.014), LV end-systolic volume (MD = 4 mL/m2, P-value = 0.033), LV mass (mean difference = 12 g/m2, P-value = 7.8 × 10-9)]. Younger individuals had larger LV end-diastolic volumes than older ages (20-40 years vs. ≥65 years: women MD = 14.0 mL/m2, men MD = 14.7 mL/m2). East Asians (Chinese, Korean, Singaporean-Chinese, n = 514) had lower LV mass than Caucasians (women: MD = 6.4 g/m2, P-value = 0.016; men: MD = 9.8 g/m2, P-value = 6.7 × 10-5). Between-study heterogeneity was high for all LV parameters despite stratification by population-related factors. Sensitivity analyses identified differences in contouring methodology, magnet strength, and post-processing software as potential sources of heterogeneity.

Conclusion

There is significant variation between CMR normal reference ranges due to multiple population-related and technical factors. Whilst there is need for population-stratified reference ranges, limited sample sizes and technical heterogeneity precludes derivation of meaningful unified ranges from existing reports. Wider representation of different populations and standardization of image analysis is urgently needed to establish such reference distributions.
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Cingulo-opercular control network and disused motor circuits joined in standby mode.

Issue 13 Vol 118 Published on 2021-03-01 PMID 33753484 PMCID PMC8020791
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Keywords: fMRI, Plasticity, Spontaneous activity, Disuse, Network Neuroscience
DOI: https://doi.org/10.1073/pnas.2019128118
Authors: Dillan J Newbold In X Evan M Gordon In X Timothy O Laumann In X Nicole A Seider In X David F Montez In X Sarah J Gross In X Annie Zheng In X Ashley N Nielsen In X Catherine R Hoyt In X Jacqueline M Hampton In X Mario Ortega In X Babatunde Adeyemo In X Derek B Miller In X Andrew N Van In X Scott Marek In X Bradley L Schlaggar In X Alexandre R Carter In X Benjamin P Kay In X Deanna J Greene In X Marcus E Raichle In X Steven E Petersen In X Abraham Z Snyder In X Nico U F Dosenbach In X
Abstract: Whole-brain resting-state functional MRI (rs-fMRI) during 2 wk of upper-limb casting revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula. Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.
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Microvascular Obstruction: How to Find the Traces of a Transient Pathology After Myocardial Infarction.

Issue 2 Vol 14 Published on 2021-02-01 PMID 33583191 PMCID N/A
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Keywords: Myocardium, Gadolinium, Myocardial infarction, Prognosis, Death, Editorials
DOI: https://doi.org/10.1161/circimaging.121.012324
Authors: Michael Jerosch-Herold In X Steffen E Petersen In X
Abstract: No Abstract Available
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Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.

Issue 2 Vol 53 Published on 2021-02-01 PMID 33495597 PMCID PMC8240954
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Keywords:
DOI: https://doi.org/10.1038/s41588-020-00764-0
Authors: Andrew R Harper In X Anuj Goel In X Christopher Grace In X Kate L Thomson In X Steffen E Petersen In X Xiao Xu In X Adam Waring In X Elizabeth Ormondroyd In X Christopher M Kramer In X Carolyn Y Ho In X Stefan Neubauer In X In X Rafik Tadros In X James S Ware In X Connie R Bezzina In X Martin Farrall In X Hugh Watkins In X
Abstract: Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.
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Cardiovascular magnetic resonance imaging in the UK Biobank: a major international health research resource.

Open Access Issue 3 Vol 22 Published on 2021-02-01 PMID 33164079 PMCID PMC7899275
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Keywords: epidemiology, Cardiovascular Magnetic Resonance, Population Health, Big Data, Uk Biobank
DOI: https://doi.org/10.1093/ehjci/jeaa297
Authors: Zahra Raisi-Estabragh In X Nicholas C Harvey In X Stefan Neubauer In X Steffen E Petersen In X
Abstract: The UK Biobank (UKB) is a health research resource of major international importance, incorporating comprehensive characterization of >500 000 men and women recruited between 2006 and 2010 from across the UK. There is prospective tracking of health outcomes for all participants through linkages with national cohorts (death registers, cancer registers, electronic hospital records, and primary care records). The dataset has been enhanced with the UKB imaging study, which aims to scan a subset of 100 000 participants. The imaging protocol includes magnetic resonance imaging of the brain, heart, and abdomen, carotid ultrasound, and whole-body dual X-ray absorptiometry. Since its launch in 2015, over 48 000 participants have completed the imaging study with scheduled completion in 2023. Repeat imaging of 10 000 participants has been approved and commenced in 2019. The cardiovascular magnetic resonance (CMR) scan provides detailed assessment of cardiac structure and function comprising bright blood anatomic assessment (sagittal, coronal, and axial), left and right ventricular cine images (long and short axes), myocardial tagging, native T1 mapping, aortic flow, and imaging of the thoracic aorta. The UKB is an open access resource available to health researchers across all scientific disciplines from both academia and industry with no preferential access or exclusivity. In this paper, we consider how we may best utilize the UKB CMR data to advance cardiovascular research and review notable achievements to date.
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2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC.

Issue 5 Vol 42 Published on 2021-02-01 PMID 32860505 PMCID N/A
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Keywords: Screening, Anticoagulation, Atrial fibrillation, Stroke, Catheter ablation, Recommendations, Guidelines, Rhythm Control, Pulmonary Vein Isolation, Cardioversion, Antiarrhythmic Drugs, Upstream Therapy, Vitamin K Antagonists, Left Atrial Ablation, Left Atrial Appendage Occlusion, Rate Control, Non-vitamin K Antagonist Oral Anticoagulants, Abc Pathway, Af Surgery
DOI: https://doi.org/10.1093/eurheartj/ehaa612
Authors: Gerhard Hindricks In X Tatjana Potpara In X Nikolaos Dagres In X Elena Arbelo In X Jeroen J Bax In X Carina Blomström-Lundqvist In X Giuseppe Boriani In X Manuel Castella In X Gheorghe-Andrei Dan In X Polychronis E Dilaveris In X Laurent Fauchier In X Gerasimos Filippatos In X Jonathan M Kalman In X Mark La Meir In X Deirdre A Lane In X Jean-Pierre Lebeau In X Maddalena Lettino In X Gregory Y H Lip In X Fausto J Pinto In X G Neil Thomas In X Marco Valgimigli In X Isabelle C Van Gelder In X Bart P Van Putte In X Caroline L Watkins In X In X
Abstract: No Abstract Available
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2020 ESC Guidelines for the management of adult congenital heart disease.

Issue 6 Vol 42 Published on 2021-02-01 PMID 32860028 PMCID N/A
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Keywords: Adult, Disease, Diagnosis, Congenital heart disease, Imaging, Recommendations, Guidelines, Medical Treatment, Late Complications, Catheter Intervention, Congenital Cardiac Surgery, Patient Follow-up
DOI: https://doi.org/10.1093/eurheartj/ehaa554
Authors: Helmut Baumgartner In X Julie De Backer In X Sonya V Babu-Narayan In X Werner Budts In X Massimo Chessa In X Gerhard-Paul Diller In X Bernard Lung In X Jolanda Kluin In X Irene M Lang In X Folkert Meijboom In X Philip Moons In X Barbara J M Mulder In X Erwin Oechslin In X Jolien W Roos-Hesselink In X Markus Schwerzmann In X Lars Sondergaard In X Katja Zeppenfeld In X In X
Abstract: No Abstract Available
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An agenda-setting paper on data sharing platforms: euCanSHare workshop.

Open Access Issue N/A Vol 1 Published on 2021-01-01 PMID 37645200 PMCID PMC10445835
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Keywords: data sharing, Incentives, Science Policy, Open Science, Data Infrastructure
DOI: https://doi.org/10.12688/openreseurope.13860.2
Authors: Thijs Devriendt In X Clemens Ammann In X Folkert W Asselbergs In X Alexander Bernier In X Rodrigo Costas In X Matthias G Friedrich In X Josep L Gelpi In X Marjo-Riitta Jarvelin In X Kari Kuulasmaa In X Karim Lekadir In X Michaela Th Mayrhofer In X Vaclav Papez In X Gerard Pasterkamp In X Steffen E Petersen In X Carsten Oliver Schmidt In X Jeanette Schulz-Menger In X Stefan Söderberg In X Mahsa Shabani In X Giovanni Veronesi In X Darian Steven Viezzer In X Pascal Borry In X
Abstract: Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.
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A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 35242820 PMCID PMC8886212
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Keywords: Quality control, Assessment, Machine Learning, Cardiac Segmentation, Cardiac Magnetic Resonance (Cmr), Automated Contouring
DOI: https://doi.org/10.3389/fcvm.2021.816985
Authors: Elisa Rauseo In X Muhammad Omer In X Alborz Amir-Khalili In X Alireza Sojoudi In X Thu-Thao Le In X Stuart Alexander Cook In X Derek John Hausenloy In X Briana Ang In X Desiree-Faye Toh In X Jennifer Bryant In X Calvin Woon Loong Chin In X Jose Miguel Paiva In X Kenneth Fung In X Jackie Cooper In X Mohammed Yunus Khanji In X Nay Aung In X Steffen Erhard Petersen In X
Abstract:

Background

The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed.

Objective

We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm.

Methods

A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease.

Results

The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension.

Conclusions

Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.
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Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 35004880 PMCID PMC8727756
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Keywords: Hypertension, Diabetes, Smoking, Sex differences, High cholesterol, Cardiovascular Magnetic Resonance, Healthy Individuals, Radiomics
DOI: https://doi.org/10.3389/fcvm.2021.763361
Authors: Zahra Raisi-Estabragh In X Akshay Jaggi In X Polyxeni Gkontra In X Celeste McCracken In X Nay Aung In X Patricia B Munroe In X Stefan Neubauer In X Nicholas C Harvey In X Karim Lekadir In X Steffen E Petersen In X
Abstract: Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters. Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed.
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A Cost Analysis of Cardiac Magnetic Resonance Imaging in the Diagnostic Pathway of Patients Presenting With Unexplained Acute Myocardial Injury and Culprit-Free Coronary Angiography.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 34746264 PMCID PMC8564112
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Keywords: Cost-benefit Analysis, Cardiac Magnetic Resonance (Cmr) Imaging, Myocardial Infarction With Non-Obstructive Coronary Atherosclerosis, Financial Modeling/Forecasting, Healthcare Planning And Management
DOI: https://doi.org/10.3389/fcvm.2021.749668
Authors: Theodore Murphy In X Daniel A Jones In X Rocco Friebel In X Ijeoma Uchegbu In X Saidi A Mohiddin In X Steffen E Petersen In X
Abstract: Aims: To determine financial implications of implementing cardiac magnetic resonance imaging (CMR) in the diagnostic pathway of a population with unexplained acute myocardial injury and normal coronary angiography. Methods and Results: We performed a focused cost-benefit analysis using a hypothetical population of 2,000 patients with unexplained acute myocardial injury and normal coronary angiography divided into two groups to receive either standard or CMR guided management over a 10-year period. As healthcare practice and costs considerably vary geographically and over time, an algorithm with 15 key variables was developed to permit user-defined calculations of cost-benefit and other analyses. Using current UK costs, routine use of CMR increases healthcare spending by 14% per patient in the first year. After 7 years, CMR guided practice is cost neutral, reducing cost by 3% per patient 10 years following presentation. In addition, CMR -guided therapy results in 7 fewer myocardial infarctions and 14 fewer major bleeding events per 1,000 patients over a 10-year period. The three most sensitive variables were, in decreasing order, the cost of CMR, the cost of ticagrelor and the percentage of the population with MI requiring DAPT. Conclusion: Routine use of CMR in patients with unexplained acute myocardial injury and normal coronary angiography is associated with cost reductions in the medium to long term. The initial higher cost of CMR is offset over time and delivers a more personalized and higher quality of care.
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New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 34631820 PMCID PMC8494975
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Keywords: Myocardial infarction, Stroke, Cerebrovascular disease, Ischaemic Heart Disease, Cardiovascular Magnetic Resonance, Radiomics, Brain-heart Axis
DOI: https://doi.org/10.3389/fcvm.2021.716577
Authors: Elisa Rauseo In X Cristian Izquierdo Morcillo In X Zahra Raisi-Estabragh In X Polyxeni Gkontra In X Nay Aung In X Karim Lekadir In X Steffen E Petersen In X
Abstract: Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.
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Automated Quality-Controlled Cardiovascular Magnetic Resonance Pericardial Fat Quantification Using a Convolutional Neural Network in the UK Biobank.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 34307493 PMCID PMC8294033
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Keywords: Obesity, Neural network, Machine Learning, Cardiovascular Magnetic Resonance, Pericardial Fat, Automated Image Analysis, Epicardial Fat
DOI: https://doi.org/10.3389/fcvm.2021.677574
Authors: Andrew Bard In X Zahra Raisi-Estabragh In X Maddalena Ardissino In X Aaron Mark Lee In X Francesca Pugliese In X Damini Dey In X Sandip Sarkar In X Patricia B Munroe In X Stefan Neubauer In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract: Background: Pericardial adipose tissue (PAT) may represent a novel risk marker for cardiovascular disease. However, absence of rapid radiation-free PAT quantification methods has precluded its examination in large cohorts. Objectives: We developed a fully automated quality-controlled tool for cardiovascular magnetic resonance (CMR) PAT quantification in the UK Biobank (UKB). Methods: Image analysis comprised contouring an en-bloc PAT area on four-chamber cine images. We created a ground truth manual analysis dataset randomly split into training and test sets. We built a neural network for automated segmentation using a Multi-residual U-net architecture with incorporation of permanently active dropout layers to facilitate quality control of the model's output using Monte Carlo sampling. We developed an in-built quality control feature, which presents predicted Dice scores. We evaluated model performance against the test set (n = 87), the whole UKB Imaging cohort (n = 45,519), and an external dataset (n = 103). In an independent dataset, we compared automated CMR and cardiac computed tomography (CCT) PAT quantification. Finally, we tested association of CMR PAT with diabetes in the UKB (n = 42,928). Results: Agreement between automated and manual segmentations in the test set was almost identical to inter-observer variability (mean Dice score = 0.8). The quality control method predicted individual Dice scores with Pearson r = 0.75. Model performance remained high in the whole UKB Imaging cohort and in the external dataset, with medium-good quality segmentation in 94.3% (mean Dice score = 0.77) and 94.4% (mean Dice score = 0.78), respectively. There was high correlation between CMR and CCT PAT measures (Pearson r = 0.72, p-value 5.3 ×10-18). Larger CMR PAT area was associated with significantly greater odds of diabetes independent of age, sex, and body mass index. Conclusions: We present a novel fully automated method for CMR PAT quantification with good model performance on independent and external datasets, high correlation with reference standard CCT PAT measurement, and expected clinical associations with diabetes.
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COVID-19 and the Digitalisation of Cardiovascular Training and Education-A Review of Guiding Themes for Equitable and Effective Post-graduate Telelearning.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 34277728 PMCID PMC8283504
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Keywords: Education, Telemedicine, Equity In Access, Diversity And Inclusion, Digitalisation, Covid-19, Elearning (Web-Based Learning/Distance Learning), Simulation Based Teaching
DOI: https://doi.org/10.3389/fcvm.2021.666119
Authors: Jun Hua Chong In X C Anwar A Chahal In X Ajay Gupta In X Fabrizio Ricci In X Mark Westwood In X Francesca Pugliese In X Steffen E Petersen In X Mohammed Y Khanji In X
Abstract: The coronavirus disease-2019 (COVID-19) pandemic has had an unprecedented impact leading to novel adaptations in post-graduate medical education for cardiovascular and general internal medicine. Whilst the results of initial community COVID-19 vaccination are awaited, continuation of multimodality teaching and training that incorporates telelearning will have enduring benefit to post-graduate education and will place educational establishments in good stead to nimbly respond in future pandemic-related public health emergencies. With the rise in innovative virtual learning solutions, medical educators will have to leverage technology to develop electronic educational materials and virtual courses that facilitate adult learning. Technology-enabled virtual learning is thus a timely progression of hybrid classroom initiatives that are already adopted to varying degrees, with a need for faculty to serve as subject matter experts, to host and moderate online discussions, and to provide feedback and overall mentorship. As an extension from existing efforts, simulation-based teaching (SBT) and learning and the use of mixed reality technology should also form a greater core in the cardiovascular medicine curriculum. We highlight five foundational themes for building a successful e-learning model in cardiovascular and general post-graduate medical training: (1) digital solutions and associated infrastructure; (2) equity in access; (3) participant engagement; (4) diversity and inclusion; and (5) patient confidentiality and governance framework. With digitalisation impacting our everyday lives and now how we teach and train in medicine, these five guiding principles provide a cognitive scaffold for careful consideration of the required ecosystem in which cardiovascular and general post-graduate medical education can effectively operate. With due consideration of various e-learning options and associated infrastructure needs; and adoption of strategies for participant engagement under sound and just governance, virtual training in medicine can be effective, inclusive and equitable through the COVID-19 era and beyond.
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Androgen Deprivation Therapy Combined With Particle Therapy for Prostate Cancer: A Systematic Review.

Open Access Issue N/A Vol 11 Published on 2021-01-01 PMID 34249753 PMCID PMC8260995
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Keywords: Androgen deprivation therapy, prostate cancer, Overall Survival, Proton Therapy, Carbon Ion Therapy, Biochemical Disease-free Survival, Late Morbidity, Acute Morbidity
DOI: https://doi.org/10.3389/fonc.2021.695647
Authors: Stine Elleberg Petersen In X Morten Høyer In X
Abstract:

Purpose

There is high-level evidence for addition of androgen deprivation therapy to photon-based radiotherapy of the prostate in intermediate- and high-risk prostate cancer. Little is known about the value of ADT in particle therapy of prostate cancer. We are conducting a systematic review on biochemical disease-free survival, overall survival, and morbidity after combined particle therapy and ADT for prostate cancer.

Methods

A thorough search in PubMed, Embase, Scopus, and Web of Science databases were conducted, searching for relevant studies. Clinical studies on prostate cancer and the treatment combination of particle therapy and androgen deprivation therapy were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD42021230801).

Results

A total of 298 papers were identified. Fifteen papers reporting on 7,202 patients after proton or carbon-ion therapy for localized prostate cancer where a fraction or all patients received ADT were selected for analysis. Three thousand five hundred and nineteen (49%) of the patients had received combined ADT and particle therapy. Primarily high-risk (87%), to a lesser extent intermediate-risk (34%) and low-risk patients (12%) received ADT. There were no comparative studies on the effect of ADT in patients treated with particles and no studies identified ADT as an independent prognostic factor related to survival outcomes.

Conclusions

The review found no evidence to support that the effects on biochemical disease-free survival and morbidity of combining ADT to particle therapy differs from the ADT effects in conventional photon based radiotherapy. The available data on the topic is limited.
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The Promise of AI in Detection, Diagnosis, and Epidemiology for Combating COVID-19: Beyond the Hype.

Open Access Issue N/A Vol 4 Published on 2021-01-01 PMID 34056579 PMCID PMC8160471
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Keywords: Artificial intelligence, Detection, Diagnosis, Medical imaging, epidemiology, Contact tracing, Social Control, Covid-19
DOI: https://doi.org/10.3389/frai.2021.652669
Authors: Musa Abdulkareem In X Steffen E Petersen In X
Abstract: COVID-19 has created enormous suffering, affecting lives, and causing deaths. The ease with which this type of coronavirus can spread has exposed weaknesses of many healthcare systems around the world. Since its emergence, many governments, research communities, commercial enterprises, and other institutions and stakeholders around the world have been fighting in various ways to curb the spread of the disease. Science and technology have helped in the implementation of policies of many governments that are directed toward mitigating the impacts of the pandemic and in diagnosing and providing care for the disease. Recent technological tools, artificial intelligence (AI) tools in particular, have also been explored to track the spread of the coronavirus, identify patients with high mortality risk and diagnose patients for the disease. In this paper, areas where AI techniques are being used in the detection, diagnosis and epidemiological predictions, forecasting and social control for combating COVID-19 are discussed, highlighting areas of successful applications and underscoring issues that need to be addressed to achieve significant progress in battling COVID-19 and future pandemics. Several AI systems have been developed for diagnosing COVID-19 using medical imaging modalities such as chest CT and X-ray images. These AI systems mainly differ in their choices of the algorithms for image segmentation, classification and disease diagnosis. Other AI-based systems have focused on predicting mortality rate, long-term patient hospitalization and patient outcomes for COVID-19. AI has huge potential in the battle against the COVID-19 pandemic but successful practical deployments of these AI-based tools have so far been limited due to challenges such as limited data accessibility, the need for external evaluation of AI models, the lack of awareness of AI experts of the regulatory landscape governing the deployment of AI tools in healthcare, the need for clinicians and other experts to work with AI experts in a multidisciplinary context and the need to address public concerns over data collection, privacy, and protection. Having a dedicated team with expertise in medical data collection, privacy, access and sharing, using federated learning whereby AI scientists hand over training algorithms to the healthcare institutions to train models locally, and taking full advantage of biomedical data stored in biobanks can alleviate some of problems posed by these challenges. Addressing these challenges will ultimately accelerate the translation of AI research into practical and useful solutions for combating pandemics.
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Associations of Meat and Fish Consumption With Conventional and Radiomics Cardiovascular Magnetic Resonance Phenotypes in the UK Biobank.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 34026874 PMCID PMC8133433
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Keywords: Diet, Cardiovascular disease, Meat, Disease Prevention, Cardiovascular Magnetic Resonance, Population Health, Radiomics
DOI: https://doi.org/10.3389/fcvm.2021.667849
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Polyxeni Gkontra In X Akshay Jaggi In X Maddalena Ardissino In X Jackie Cooper In X Luca Biasiolli In X Nay Aung In X Stefan K Piechnik In X Stefan Neubauer In X Patricia B Munroe In X Karim Lekadir In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract: Background: Greater red and processed meat consumption has been linked to adverse cardiovascular outcomes. However, the impact of these exposures on cardiovascular magnetic resonance (CMR) phenotypes has not been adequately studied. Objective: We describe novel associations of meat intake with cardiovascular phenotypes and investigate underlying mechanisms through consideration of a range of covariates. Design: We studied 19,408 UK Biobank participants with CMR data available. Average daily red and processed meat consumption was determined through food frequency questionnaires and expressed as a continuous variable. Oily fish was studied as a comparator, previously associated with favourable cardiac outcomes. We considered associations with conventional CMR indices (ventricular volumes, ejection fraction, stroke volume, left ventricular mass), novel CMR radiomics features (shape, first-order, texture), and arterial compliance measures (arterial stiffness index, aortic distensibility). We used multivariable linear regression to investigate relationships between meat intake and cardiovascular phenotypes, adjusting for confounders (age, sex, deprivation, educational level, smoking, alcohol intake, exercise) and potential covariates on the causal pathway (hypertension, hypercholesterolaemia, diabetes, body mass index). Results: Greater red and processed meat consumption was associated with an unhealthy pattern of biventricular remodelling, worse cardiac function, and poorer arterial compliance. In contrast, greater oily fish consumption was associated with a healthier cardiovascular phenotype and better arterial compliance. There was partial attenuation of associations between red meat and conventional CMR indices with addition of covariates potentially on the causal pathway, indicating a possible mechanistic role for these cardiometabolic morbidities. However, other associations were not altered with inclusion of these covariates, suggesting importance of alternative biological mechanisms underlying these relationships. Radiomics analysis provided deeper phenotyping, demonstrating association of the different dietary habits with distinct ventricular geometry and left ventricular myocardial texture patterns. Conclusions: Greater red and processed meat consumption is associated with impaired cardiovascular health, both in terms of markers of arterial disease and of cardiac structure and function. Cardiometabolic morbidities appeared to have a mechanistic role in the associations of red meat with ventricular phenotypes, but less so for other associations suggesting importance of alternative mechanism for these relationships.
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Women With Diabetes Are at Increased Relative Risk of Heart Failure Compared to Men: Insights From UK Biobank.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 33889602 PMCID PMC8057521
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Keywords: Sex, Prognosis, Diabetes, epidemiology, Heart Failure, cardiovascular, Prospective, Uk Biobank
DOI: https://doi.org/10.3389/fcvm.2021.658726
Authors: Sucharitha Chadalavada In X Magnus T Jensen In X Nay Aung In X Jackie Cooper In X Karim Lekadir In X Patricia B Munroe In X Steffen E Petersen In X
Abstract: Aims: To investigate the effect of diabetes on mortality and incident heart failure (HF) according to sex, in the low risk population of UK Biobank. To evaluate potential contributing factors for any differences seen in HF end-point. Methods: The entire UK Biobank study population were included. Participants that withdrew consent or were diagnosed with diabetes after enrolment were excluded from the study. Univariate and multivariate cox regression models were used to assess endpoints of mortality and incident HF, with median follow-up periods of 9 years and 8 years respectively. Results: A total of 493,167 participants were included, hereof 22,685 with diabetes (4.6%). Two thousand four hundred fifty four died and 1,223 were diagnosed or admitted with HF during the follow up periods of 9 and 8 years respectively. Overall, the mortality and HF risk were almost doubled in those with diabetes compared to those without diabetes (hazard ratio (HR) of 1.9 for both mortality and heart failure) in the UK Biobank population. Women with diabetes (both types) experience a 22% increased risk of HF compared to men (HR of 2.2 (95% CI: 1.9-2.5) vs. 1.8 (1.7-2.0) respectively). Women with type 1 diabetes (T1DM) were associated with 88% increased risk of HF compared to men (HR 4.7 (3.6-6.2) vs. 2.5 (2.0-3.0) respectively), while the risk of HF for type 2 diabetes (T2DM) was 17% higher in women compared to men (2.0 (1.7-2.3) vs. 1.7 (1.6-1.9) respectively). The increased risk of HF in women was independent of confounding factors. The findings were similar in a model with all-cause mortality as a competing risk. This interaction between sex, diabetes and outcome of HF is much more prominent for T1DM (p = 0.0001) than T2DM (p = 0.1). Conclusion: Women with diabetes, particularly those with T1DM, experience a greater increase in risk of heart failure compared to men with diabetes, which cannot be explained by the increased prevalence of cardiac risk factors in this cohort.
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Vasodilator Myocardial Perfusion Cardiac Magnetic Resonance Imaging Is Superior to Dobutamine Stress Echocardiography in the Detection of Relevant Coronary Artery Stenosis: A Systematic Review and Meta-Analysis on Their Diagnostic Accuracy.

Open Access Issue N/A Vol 8 Published on 2021-01-01 PMID 33778024 PMCID PMC7994268
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Keywords: Meta-analysis, Dobutamine stress echocardiography, coronary artery disease, Cardiac Mr, Cardiac Imaging, Diagnostic Test Accuracy, Myocardial Perfusion Mr, Systematic (Literature) Review
DOI: https://doi.org/10.3389/fcvm.2021.630846
Authors: Sebastian M Haberkorn In X Sandra I Haberkorn In X Florian Bönner In X Malte Kelm In X Gareth Hopkin In X Steffen E Petersen In X
Abstract: Objectives: Guideline recommendations for patients with either a high or a low risk of obstructive coronary artery disease (CAD) are clear. However, the evidence for initial risk stratification in patients with an intermediate risk of CAD is still unclear, despite the availability of multiple non-invasive assessment strategies. The aim of this study was to synthesize the evidence for this population to provide more informed recommendations. Background: A meta-analysis was performed to systematically assess the diagnostic accuracy of vasodilator myocardial perfusion cardiovascular magnetic resonance imaging (pCMR) and dobutamine stress echocardiography (DSE) for the detection of relevant CAD. In contrast to previous work, this meta-analysis follows rigorous selection criteria in regards to the risk stratification and a narrowly prespecified definition of their invasive reference tests, resulting in unprecedentedly informative results for this reference group. Data Collection and Analysis: From the 5,634 studies identified, 1,306 relevant articles were selected after title screening and further abstract screening left 865 studies for full-text review. Of these, 47 studies fulfilled all inclusion criteria resulting in a total sample size of 4,742 patients. Results: pCMR studies showed a superior sensitivity [0.88 (95% confidence interval (CI): 0.85-0.90) vs. 0.72 (95% CI: 0.61-0.81)], diagnostic odds ratio (DOR) [38 (95% CI: 29-49) vs. 20 (95% CI: 9-46)] and an augmented post-test probability [negative likelihood ratio (LR) of 0.14 (95% CI: 0.12-0.18) vs. 0.31 (95% CI: 0.21, 0.46)] as compared to DSE. Specificity was statistically indifferent [0.84 (95% CI: 0.81-0.87) vs. 0.89 (95% CI: 0.83-0.93)]. Conclusion: The results of this systematic review and meta-analysis suggest that pCMR has a superior diagnostic test accuracy for relevant CAD compared to DSE. In patients with intermediate risk of CAD only pCMR can reliably rule out relevant stenosis. In this risk cohort, pCMR can be offered for initial risk stratification and guidance of further invasive treatment as it also rules in relevant CAD.
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Diagnosis and risk stratification in hypertrophic cardiomyopathy using machine learning wall thickness measurement: a comparison with human test-retest performance.

Issue 1 Vol 3 Published on 2021-01-01 PMID 33735065 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/s2589-7500(20)30267-3
Authors: João B Augusto In X Rhodri H Davies In X Anish N Bhuva In X Kristopher D Knott In X Andreas Seraphim In X Mashael Alfarih In X Clement Lau In X Rebecca K Hughes In X Luís R Lopes In X Hunain Shiwani In X Thomas A Treibel In X Bernhard L Gerber In X Christian Hamilton-Craig In X Ntobeko A B Ntusi In X Gianluca Pontone In X Milind Y Desai In X John P Greenwood In X Peter P Swoboda In X Gabriella Captur In X João Cavalcante In X Chiara Bucciarelli-Ducci In X Steffen E Petersen In X Erik Schelbert In X Charlotte Manisty In X James C Moon In X
Abstract:

Background

Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy, but human measurement is prone to variability. We developed an automated machine learning algorithm for MWT measurement and compared precision (reproducibility) with that of 11 international experts, using a dataset of patients with hypertrophic cardiomyopathy.

Methods

60 adult patients with hypertrophic cardiomyopathy, including those carrying hypertrophic cardiomyopathy gene mutations, were recruited at three institutes in the UK from August, 2018, to September, 2019: Barts Heart Centre, University College London Hospital (The Heart Hospital), and Leeds Teaching Hospitals NHS Trust. Participants had two cardiovascular magnetic resonance scans (test and retest) on the same day, ensuring no biological variability, using four cardiac MRI scanner models represented across two manufacturers and two field strengths. End-diastolic short-axis MWT was measured in test and retest by 11 international experts (from nine centres in six countries) and an automated machine learning method, which was trained to segment endocardial and epicardial contours on an independent, multicentre, multidisease dataset of 1923 patients. Machine learning MWT measurement was done with a method based on solving Laplace's equation. To assess test-retest reproducibility, we estimated the absolute test-retest MWT difference (precision), the coefficient of variation (CoV) for duplicate measurements, and the number of patients reclassified between test and retest according to different thresholds (MWT >15 mm and >30 mm). We calculated the sample size required to detect a prespecified MWT change between pairs of scans for machine learning and each expert.

Findings

1440 MWT measurements were analysed, corresponding to two scans from 60 participants by 12 observers (11 experts and machine learning). Experts differed in the MWT they measured, ranging from 14·9 mm (SD 4·2) to 19·0 mm (4·7; p<0·0001 for trend). Machine learning-measured mean MWT was 16·8 mm (4·1). Machine learning precision was superior, with a test-retest difference of 0·7 mm (0·6) compared with experts, who ranged from 1·1 mm (0·9) to 3·7 mm (2·0; p values for machine learning vs expert comparison ranging from <0·0001 to 0·0073) and a significantly lower CoV than for all experts (4·3% [95% CI 3·3-5·1] vs 5·7-12·1% across experts). On average, 38 (64%) patients were designated as having MWT greater than 15 mm by machine learning compared with 27 (45%) to 50 (83%) patients by experts; five (8%) patients were reclassified in test-retest by machine learning compared with four (7%) to 12 (20%) by experts. With a cutoff point of more than 30 mm for implantable cardioverter-defibrillator, three experts would have changed recommendations between tests a total of four times, but machine learning was consistent. Using machine learning, a clinical trial to detect a 2 mm MWT change would need 2·3 times (range 1·6-4·6) fewer patients.

Interpretation

In this preliminary study, machine learning MWT measurement in hypertrophic cardiomyopathy is superior to human experts with potential implications for diagnosis, risk stratification, and clinical trials.

Funding

European Regional Development Fund and Barts Charity.
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Recovering from missing data in population imaging - Cardiac MR image imputation via conditional generative adversarial nets.

Issue N/A Vol 67 Published on 2021-01-01 PMID 33129140 PMCID N/A
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Keywords: Cardiac Mri, Data Imputation, Deep Learning, Multi-scale Discriminator, Conditional Batch Normalisation, Conditional Generative Adversarial Net
DOI: https://doi.org/10.1016/j.media.2020.101812
Authors: Yan Xia In X Le Zhang In X Nishant Ravikumar In X Rahman Attar In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: Accurate ventricular volume measurements are the primary indicators of normal/abnor- mal cardiac function and are dependent on the Cardiac Magnetic Resonance (CMR) volumes being complete. However, missing or unusable slices owing to the presence of image artefacts such as respiratory or motion ghosting, aliasing, ringing and signal loss in CMR sequences, significantly hinder accuracy of anatomical and functional cardiac quantification, and recovering from those is insufficiently addressed in population imaging. In this work, we propose a new robust approach, coined Image Imputation Generative Adversarial Network (I2-GAN), to learn key features of cardiac short axis (SAX) slices near missing information, and use them as conditional variables to infer missing slices in the query volumes. In I2-GAN, the slices are first mapped to latent vectors with position features through a regression net. The latent vector corresponding to the desired position is then projected onto the slice manifold, conditioned on intensity features through a generator net. The generator comprises residual blocks with normalisation layers that are modulated with auxiliary slice information, enabling propagation of fine details through the network. In addition, a multi-scale discriminator was implemented, along with a discriminator-based feature matching loss, to further enhance performance and encourage the synthesis of visually realistic slices. Experimental results show that our method achieves significant improvements over the state-of-the-art, in missing slice imputation for CMR, with an average SSIM of 0.872. Linear regression analysis yields good agreement between reference and imputed CMR images for all cardiac measurements, with correlation coefficients of 0.991 for left ventricular volume, 0.977 for left ventricular mass and 0.961 for right ventricular volume.
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Poor Bone Quality is Associated With Greater Arterial Stiffness: Insights From the UK Biobank.

Open Access Issue 1 Vol 36 Published on 2021-01-01 PMID 32964541 PMCID PMC7613252
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Keywords: Osteoporosis, Cardiovascular disease, ischemic heart disease, epidemiology, Arterial stiffness
DOI: https://doi.org/10.1002/jbmr.4164
Authors: Zahra Raisi-Estabragh In X Luca Biasiolli In X Jackie Cooper In X Nay Aung In X Kenneth Fung In X José M Paiva In X Mihir M Sanghvi In X Ross J Thomson In X Elizabeth Curtis In X Julien Paccou In X Jennifer J Rayner In X Konrad Werys In X Henrike Puchta In X Katharine E Thomas In X Aaron M Lee In X Stefan K Piechnik In X Stefan Neubauer In X Patricia B Munroe In X Cyrus Cooper In X Steffen E Petersen In X Nicholas C Harvey In X
Abstract: Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease.

Issue 1 Vol 42 Published on 2021-01-01 PMID 32860412 PMCID N/A
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Keywords: Pregnancy, Cancer, Exercise, Cardiomyopathy, Arrhythmias, Cardiovascular risk factors, Risk stratification, Heart Failure, Recommendations, Guidelines, Valvular Heart Disease, Peripheral Vascular Disease, Adult Congenital Heart Disease, Aortopathies, Chronic Coronary Syndromes, Sport – Special Environments
DOI: https://doi.org/10.1093/eurheartj/ehaa605
Authors: Antonio Pelliccia In X Sanjay Sharma In X Sabiha Gati In X Maria Bäck In X Mats Börjesson In X Stefano Caselli In X Jean-Philippe Collet In X Domenico Corrado In X Jonathan A Drezner In X Martin Halle In X Dominique Hansen In X Hein Heidbuchel In X Jonathan Myers In X Josef Niebauer In X Michael Papadakis In X Massimo Francesco Piepoli In X Eva Prescott In X Jolien W Roos-Hesselink In X A Graham Stuart In X Rod S Taylor In X Paul D Thompson In X Monica Tiberi In X Luc Vanhees In X Matthias Wilhelm In X In X
Abstract: No Abstract Available
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Amygdala Functional Connectivity Is Associated With Emotion Regulation and Amygdala Reactivity in 4- to 6-Year-Olds.

Issue 1 Vol 60 Published on 2021-01-01 PMID 32119912 PMCID PMC7483219
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Keywords: Amygdala, Pediatric, Emotion Regulation, Functional Connectivity, Irritability
DOI: https://doi.org/10.1016/j.jaac.2020.01.024
Authors: Michael S Gaffrey In X Deanna M Barch In X Joan L Luby In X Steven E Petersen In X
Abstract:

Objective

Emotion dysregulation has been suggested to be a potent risk factor for multiple psychiatric conditions. Altered amygdala-prefrontal cortex (PFC) connectivity has been consistently linked to emotion dysregulation. Recent data indicate that amygdala-PFC functional connectivity undergoes a prolonged period of development, with amygdala reactivity during early childhood potentially shaping this unfolding process. Little is known about the relationships between amygdala-PFC functional connectivity, amygdala reactivity, and emotion regulation during early childhood. This information is likely critical for understanding early emotion dysregulation as a transdiagnostic risk factor for psychopathology. The current study examined the relationships between amygdala functional connectivity, amygdala reactivity, and emotion regulation in preschoolers.

Method

A total of 66 medication-naive 4- to 6-year-olds participated in a study where resting-state functional magnetic resonance imaging (rs-fMRI) and parent-reported child emotion regulation ability data were collected. fMRI data collected during a face viewing task was also available for 24 children.

Results

Right amygdala-medial PFC (mPFC) functional connectivity was positively associated with child emotion regulation ability and negatively associated with child negative affect and right amygdala reactivity to facial expressions of emotion. Right amygdala-mPFC functional connectivity also statistically mediated the relationship between heightened right amygdala reactivity and elevated child negative affect.

Conclusion

Study findings suggest that amygdala-mPFC functional connectivity during early childhood, and its relationships with amygdala reactivity and emotion regulation during this highly sensitive developmental period, may play an important role in early emotional development. These results inform the neurodevelopmental biology of emotion regulation and its potential relationship with risk for psychopathology.
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Cardiovascular magnetic resonance reference values of mitral and tricuspid annular dimensions: the UK Biobank cohort.

Open Access Issue 1 Vol 23 Published on 2020-12-01 PMID 33407573 PMCID PMC7788733
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Keywords: Reference values, Mitral valve, Tricuspid valve, Cardiovascular Magnetic Resonance, Annulus, Tethering, Tenting Area
DOI: https://doi.org/10.1186/s12968-020-00688-y
Authors: Fabrizio Ricci In X Nay Aung In X Sabina Gallina In X Filip Zemrak In X Kenneth Fung In X Giandomenico Bisaccia In X Jose Miguel Paiva In X Mohammed Y Khanji In X Cesare Mantini In X Stefano Palermi In X Aaron M Lee In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults.

Methods

5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45-54, 55-64, 65-74 years).

Results

Overall, 721 (14.2%) truly healthy participants aged 45-74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m2) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m2) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m2) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m2) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m2) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m2) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m2) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m2) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97.

Conclusions

We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.
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Identify, Intervene, Improve: Tailored Cardovascular Magnetic Resonance Imaging Use Post-ST-segment-Elevation Myocardial Infarction.

Issue 12 Vol 13 Published on 2020-12-01 PMID 33297763 PMCID N/A
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Keywords: Biomarker, Echocardiography, Heart Failure, Magnetic Resonance Imaging, Editorials
DOI: https://doi.org/10.1161/circimaging.120.012084
Authors: Theodore M Murphy In X Steffen E Petersen In X
Abstract: No Abstract Available
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The Effect of Blood Lipids on the Left Ventricle: A Mendelian Randomization Study.

Open Access Issue 21 Vol 76 Published on 2020-11-01 PMID 33213727 PMCID PMC7613249
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Keywords: Lipids, Cholesterol, Cardiac remodeling, Cardiovascular Risk, Mendelian Randomization
DOI: https://doi.org/10.1016/j.jacc.2020.09.583
Authors: Nay Aung In X Mihir M Sanghvi In X Stefan K Piechnik In X Stefan Neubauer In X Patricia B Munroe In X Steffen E Petersen In X
Abstract:

Background

Cholesterol and triglycerides are among the most well-known risk factors for cardiovascular disease.

Objectives

This study investigated whether higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol level are causal risk factors for changes in prognostically important left ventricular (LV) parameters.

Methods

One-sample Mendelian randomization (MR) of 17,311 European individuals from the UK Biobank with paired lipid and cardiovascular magnetic resonance data was performed. Two-sample MR was performed by using summary-level data from the Global Lipid Genetics Consortium (n = 188,577) and UK Biobank Cardiovascular Magnetic Resonance substudy (n = 16,923) for sensitivity analyses.

Results

In 1-sample MR analysis, higher LDL cholesterol was causally associated with higher LV end-diastolic volume (β = 1.85 ml; 95% confidence interval [CI]: 0.59 to 3.14 ml; p = 0.004) and higher LV mass (β = 0.81 g; 95% CI: 0.11 to 1.51 g; p = 0.023) and triglycerides with higher LV mass (β = 1.37 g; 95% CI: 0.45 to 2.3 g; p = 0.004). High-density lipoprotein cholesterol had no significant association with any LV parameter. Similar results were obtained by using 2-sample MR. Observational analyses were frequently discordant with those derived from MR.

Conclusions

MR analysis demonstrates that LDL cholesterol and triglycerides are associated with adverse changes in cardiac structure and function, in particular in relation to LV mass. These findings suggest that LDL cholesterol and triglycerides may have a causal effect in influencing cardiac morphology in addition to their established role in atherosclerosis.
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Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction.

Issue N/A Vol 73 Published on 2020-11-01 PMID 32853757 PMCID PMC7613251
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Keywords:
DOI: https://doi.org/10.1016/j.mri.2020.08.008
Authors: Sara Doimo In X Fabrizio Ricci In X Nay Aung In X Jackie Cooper In X Redha Boubertakh In X Mihir M Sanghvi In X Gianfranco Sinagra In X Steffen E Petersen In X
Abstract:

Purpose

To test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA).

Methods

We selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters.

Results

Overall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (-20.1 ± 3.1% vs -21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (-19.7 ± 2.9% vs -21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was -21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was -16.4%.

Conclusions

At CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.
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Correction: Brain structure in pediatric Tourette syndrome.

Issue 11 Vol 25 Published on 2020-11-01 PMID 30842575 PMCID PMC7962570
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Keywords:
DOI: https://doi.org/10.1038/s41380-019-0382-8
Authors: D J Greene In X A C Williams In X J M Koller In X B L Schlaggar In X K J Black In X In X
Abstract: In this published article, members of 'The Tourette Association of America Neuroimaging Consortium' were not cited in PubMed. These consortium members are listed in the associated correction.
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Brain function distinguishes female carriers and non-carriers of familial risk for autism.

Open Access Issue 1 Vol 11 Published on 2020-10-01 PMID 33081838 PMCID PMC7574590
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Keywords: Sex ratio, Familial Risk, Biological Motion, Endophenotype, Silent Transmission
DOI: https://doi.org/10.1186/s13229-020-00381-y
Authors: Adam T Eggebrecht In X Ally Dworetsky In X Zoë Hawks In X Rebecca Coalson In X Babatunde Adeyemo In X Savannah Davis In X Daniel Gray In X Alana McMichael In X Steven E Petersen In X John N Constantino In X John R Pruett In X
Abstract:

Background

Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.

Methods

Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays-depicting biological versus non-biological motion-in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females-i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm.

Results

We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies.

Limitations

We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position.

Conclusions

These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD.
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Stress myocardial perfusion with qualitative magnetic resonance and quantitative dynamic computed tomography: comparison of diagnostic performance and incremental value over coronary computed tomography angiography.

Issue N/A Vol N/A Published on 2020-10-01 PMID 33029616 PMCID N/A
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Keywords: Myocardial perfusion, Myocardial blood flow, computed tomography, Cardiovascular Magnetic Resonance, Dynamic Perfusion
DOI: https://doi.org/10.1093/ehjci/jeaa270
Authors: Martina C de Knegt In X Alexia Rossi In X Steffen E Petersen In X Andrew Wragg In X Ruhaid Khurram In X Mark Westwood In X Bunny Saberwal In X Anthony Mathur In X Koen Nieman In X Fabian Bamberg In X Magnus T Jensen In X Francesca Pugliese In X
Abstract:

Aims

Assessment of haemodynamically significant coronary artery disease (CAD) using cardiovascular magnetic resonance (CMR) imaging perfusion or dynamic stress myocardial perfusion imaging by computed tomography (CT perfusion) may aid patient selection for invasive coronary angiography (ICA). We evaluated the diagnostic performance and incremental value of qualitative CMR perfusion and quantitative CT perfusion complementary to cardiac computed tomography angiography (CCTA) for the diagnosis of haemodynamically significant CAD using fractional flow reserve (FFR) and quantitative coronary angiography (QCA) as reference standard.

Methods and results

CCTA, qualitative visual CMR perfusion, visual CT perfusion, and quantitative relative myocardial blood flow (CT-MBF) were performed in patients with stable angina pectoris. FFR was measured in coronary vessels with stenosis visually estimated between 30% and 90% diameter reduction on ICA. Haemodynamically significant CAD was defined as FFR <0.80, or QCA ≥80% in those cases where FFR could not be performed. A total of 218 vessels from 93 patients were assessed. An optimal cut-off of 0.72 for relative CT-MBF was determined. The diagnostic performances (area under the receiver-operating characteristics curves, 95% CI) of visual CMR perfusion (0.84, 0.77-0.90) and relative CT-MBF (0.86, 0.81-0.92) were comparable and outperformed visual CT perfusion (0.64, 0.57-0.71). In combination with CCTA ≥50%, CCTA + visual CMR perfusion (0.91, 0.86-0.96), CCTA + relative CT-MBF (0.92, 0.88-0.96), and CCTA + visual CT perfusion (0.82, 0.75-0.90) improved discrimination compared with CCTA alone (all P < 0.05).

Conclusion

Visual CMR perfusion and relative CT-MBF outperformed visual CT perfusion and provided incremental discrimination compared with CCTA alone for the diagnosis of haemodynamically significant CAD.
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The year 2019 in the European Heart Journal-Cardiovascular Imaging: Part I.

Issue 11 Vol 21 Published on 2020-10-01 PMID 32929466 PMCID N/A
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Keywords: Echocardiography, Computer tomography, Nuclear Cardiology, Cardiac Magnetic Resonance
DOI: https://doi.org/10.1093/ehjci/jeaa259
Authors: Thor Edvardsen In X Kristina H Haugaa In X Steffen E Petersen In X Alessia Gimelli In X Erwan Donal In X Gerald Maurer In X Bogdan A Popescu In X Bernard Cosyns In X
Abstract: The European Heart Journal-Cardiovascular Imaging was launched in 2012 and has during these years become one of the leading multimodality cardiovascular imaging journals. The journal is now established as one of the top cardiovascular journals and is the most important cardiovascular imaging journal in Europe. The most important studies published in our Journal in 2019 will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
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Regional, not global, functional connectivity contributes to isolated focal dystonia.

Issue 16 Vol 95 Published on 2020-10-01 PMID 32913023 PMCID PMC7713779
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Keywords:
DOI: https://doi.org/10.1212/wnl.0000000000010791
Authors: Scott A Norris In X Aimee E Morris In X Meghan C Campbell In X Morvarid Karimi In X Babatunde Adeyemo In X Randal C Paniello In X Abraham Z Snyder In X Steven E Petersen In X Jonathan W Mink In X Joel S Perlmutter In X
Abstract:

Objective

To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort of patients with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study, we obtained resting-state MRI scans (three or four 7.3-minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], or limb [10]) and age- and sex-matched controls.

Methods

Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia n = 58, control n = 47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia, and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences.

Results

Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups.

Conclusion

Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiologic mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between patients with focal dystonia and control participants.
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A population-based phenome-wide association study of cardiac and aortic structure and function.

Issue 10 Vol 26 Published on 2020-10-01 PMID 32839619 PMCID PMC7613250
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Keywords:
DOI: https://doi.org/10.1038/s41591-020-1009-y
Authors: Wenjia Bai In X Hideaki Suzuki In X Jian Huang In X Catherine Francis In X Shuo Wang In X Giacomo Tarroni In X Florian Guitton In X Nay Aung In X Kenneth Fung In X Steffen E Petersen In X Stefan K Piechnik In X Stefan Neubauer In X Evangelos Evangelou In X Abbas Dehghan In X Declan P O'Regan In X Martin R Wilkins In X Yike Guo In X Paul M Matthews In X Daniel Rueckert In X
Abstract: Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.
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Evaluating the Sensitivity of Resting-State BOLD Variability to Age and Cognition after Controlling for Motion and Cardiovascular Influences: A Network-Based Approach.

Issue 11 Vol 30 Published on 2020-10-01 PMID 32515824 PMCID PMC7822708
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Keywords: Aging, Machine Learning, Resting-state Fmri, Bold Variability
DOI: https://doi.org/10.1093/cercor/bhaa138
Authors: Peter R Millar In X Steven E Petersen In X Beau M Ances In X Brian A Gordon In X Tammie L S Benzinger In X John C Morris In X David A Balota In X
Abstract: Recent functional magnetic resonance imaging (fMRI) studies report that moment-to-moment variability in the BOLD signal is related to differences in age and cognition and, thus, may be sensitive to age-dependent decline. However, head motion and/or cardiovascular health (CVH) may contaminate these relationships. We evaluated relationships between resting-state BOLD variability, age, and cognition, after characterizing and controlling for motion-related and cardiovascular influences, including pulse, blood pressure, BMI, and white matter hyperintensities (WMH), in a large (N = 422) resting-state fMRI sample of cognitively normal individuals (age 43-89). We found that resting-state BOLD variability was negatively related to age and positively related to cognition after maximally controlling for head motion. Age relationships also survived correction for CVH, but were greatly reduced when correcting for WMH alone. Our results suggest that network-based machine learning analyses of resting-state BOLD variability might yield reliable, sensitive measures to characterize age-related decline across a broad range of networks. Age-related differences in resting-state BOLD variability may be largely sensitive to processes related to WMH burden.
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A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies.

Issue 10 Vol 30 Published on 2020-09-01 PMID 32494823 PMCID N/A
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Keywords: Validity, Censoring, Functional Connectivity, Global Signal, Multiecho
DOI: https://doi.org/10.1093/cercor/bhaa139
Authors: Jonathan D Power In X Charles J Lynch In X Babatunde Adeyemo In X Steven E Petersen In X
Abstract: This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like "Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties". Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability.
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Plasticity and Spontaneous Activity Pulses in Disused Human Brain Circuits.

Issue 3 Vol 107 Published on 2020-08-01 PMID 32778224 PMCID PMC7419711
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Keywords: Cerebellum, fMRI, Plasticity, Spontaneous activity, Resting state, Functional Connectivity, Supplementary Motor Area, Primary Motor Cortex, Disuse, Alff, Amplitude Of Low-frequency Fluctuations
DOI: https://doi.org/10.1016/j.neuron.2020.05.007
Authors: Dillan J Newbold In X Timothy O Laumann In X Catherine R Hoyt In X Jacqueline M Hampton In X David F Montez In X Ryan V Raut In X Mario Ortega In X Anish Mitra In X Ashley N Nielsen In X Derek B Miller In X Babatunde Adeyemo In X Annie L Nguyen In X Kristen M Scheidter In X Aaron B Tanenbaum In X Andrew N Van In X Scott Marek In X Bradley L Schlaggar In X Alexandre R Carter In X Deanna J Greene In X Evan M Gordon In X Marcus E Raichle In X Steven E Petersen In X Abraham Z Snyder In X Nico U F Dosenbach In X
Abstract: To induce brain plasticity in humans, we casted the dominant upper extremity for 2 weeks and tracked changes in functional connectivity using daily 30-min scans of resting-state functional MRI (rs-fMRI). Casting caused cortical and cerebellar regions controlling the disused extremity to functionally disconnect from the rest of the somatomotor system, while internal connectivity within the disused sub-circuit was maintained. Functional disconnection was evident within 48 h, progressed throughout the cast period, and reversed after cast removal. During the cast period, large, spontaneous pulses of activity propagated through the disused somatomotor sub-circuit. The adult brain seems to rely on regular use to maintain its functional architecture. Disuse-driven spontaneous activity pulses may help preserve functionally disconnected sub-circuits.
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Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.

Open Access Issue 3 Vol 42 Published on 2020-08-01 PMID 32556213 PMCID PMC7449237
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Keywords: epidemiology, Communicable Diseases, Public Health
DOI: https://doi.org/10.1093/pubmed/fdaa095
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Mae S Bethell In X Jackie Cooper In X Cyrus Cooper In X Mark J Caulfield In X Patricia B Munroe In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Background

We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors.

Methods

We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status.

Results

There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations.

Conclusions

In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.
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Removal of high frequency contamination from motion estimates in single-band fMRI saves data without biasing functional connectivity.

Issue N/A Vol 217 Published on 2020-08-01 PMID 32325210 PMCID PMC7308220
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Keywords: Aging, fMRI, Motion, Artifacts, Functional Connectivity
DOI: https://doi.org/10.1016/j.neuroimage.2020.116866
Authors: Caterina Gratton In X Ally Dworetsky In X Rebecca S Coalson In X Babatunde Adeyemo In X Timothy O Laumann In X Gagan S Wig In X Tania S Kong In X Gabriele Gratton In X Monica Fabiani In X Deanna M Barch In X Daniel Tranel In X Oscar Miranda-Dominguez In X Damien A Fair In X Nico U F Dosenbach In X Abraham Z Snyder In X Joel S Perlmutter In X Steven E Petersen In X Meghan C Campbell In X
Abstract: Denoising fMRI data requires assessment of frame-to-frame head motion and removal of the biases motion introduces. This is usually done through analysis of the parameters calculated during retrospective head motion correction (i.e., 'motion' parameters). However, it is increasingly recognized that respiration introduces factitious head motion via perturbations of the main (B0) field. This effect appears as higher-frequency fluctuations in the motion parameters (>0.1 ​Hz, here referred to as 'HF-motion'), primarily in the phase-encoding direction. This periodicity can sometimes be obscured in standard single-band fMRI (TR 2.0-2.5 ​s) due to aliasing. Here we examined (1) how prevalent HF-motion effects are in seven single-band datasets with TR from 2.0 to 2.5 ​s and (2) how HF-motion affects functional connectivity. We demonstrate that HF-motion is more common in older adults, those with higher body mass index, and those with lower cardiorespiratory fitness. We propose a low-pass filtering approach to remove the contamination of high frequency effects from motion summary measures, such as framewise displacement (FD). We demonstrate that in most datasets this filtering approach saves a substantial amount of data from FD-based frame censoring, while at the same time reducing motion biases in functional connectivity measures. These findings suggest that filtering motion parameters is an effective way to improve the fidelity of head motion estimates, even in single band datasets. Particularly large data savings may accrue in datasets acquired in older and less fit participants.
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Machine Learning With Neuroimaging: Evaluating Its Applications in Psychiatry.

Issue 8 Vol 5 Published on 2020-08-01 PMID 31982357 PMCID PMC8746222
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Keywords: Prediction, Feature Selection, Machine Learning, Functional Connectivity, Computational Psychiatry, Neurophysiological Mechanisms
DOI: https://doi.org/10.1016/j.bpsc.2019.11.007
Authors: Ashley N Nielsen In X Deanna M Barch In X Steven E Petersen In X Bradley L Schlaggar In X Deanna J Greene In X
Abstract: Psychiatric disorders are complex, involving heterogeneous symptomatology and neurobiology that rarely involves the disruption of single, isolated brain structures. In an attempt to better describe and understand the complexities of psychiatric disorders, investigators have increasingly applied multivariate pattern classification approaches to neuroimaging data and in particular supervised machine learning methods. However, supervised machine learning approaches also come with unique challenges and trade-offs, requiring additional study design and interpretation considerations. The goal of this review is to provide a set of best practices for evaluating machine learning applications to psychiatric disorders. We discuss how to evaluate two common efforts: 1) making predictions that have the potential to aid in diagnosis, prognosis, and treatment and 2) interrogating the complex neurophysiological mechanisms underlying psychopathology. We focus here on machine learning as applied to functional connectivity with magnetic resonance imaging, as an example to ground discussion. We argue that for machine learning classification to have translational utility for individual-level predictions, investigators must ensure that the classification is clinically informative, independent of confounding variables, and appropriately assessed for both performance and generalizability. We contend that shedding light on the complex mechanisms underlying psychiatric disorders will require consideration of the unique utility, interpretability, and reliability of the neuroimaging features (e.g., regions, networks, connections) identified from machine learning approaches. Finally, we discuss how the rise of large, multisite, publicly available datasets may contribute to the utility of machine learning approaches in psychiatry.
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Default-mode network streams for coupling to language and control systems.

Issue 29 Vol 117 Published on 2020-07-01 PMID 32632019 PMCID PMC7382234
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Keywords: fMRI, Functional Connectivity, Brain Networks, Default Network, Individual Variability
DOI: https://doi.org/10.1073/pnas.2005238117
Authors: Evan M Gordon In X Timothy O Laumann In X Scott Marek In X Ryan V Raut In X Caterina Gratton In X Dillan J Newbold In X Deanna J Greene In X Rebecca S Coalson In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X Nico U F Dosenbach In X Steven M Nelson In X
Abstract: The human brain is organized into large-scale networks identifiable using resting-state functional connectivity (RSFC). These functional networks correspond with broad cognitive domains; for example, the Default-mode network (DMN) is engaged during internally oriented cognition. However, functional networks may contain hierarchical substructures corresponding with more specific cognitive functions. Here, we used individual-specific precision RSFC to test whether network substructures could be identified in 10 healthy human brains. Across all subjects and networks, individualized network subdivisions were more valid-more internally homogeneous and better matching spatial patterns of task activation-than canonical networks. These measures of validity were maximized at a hierarchical scale that contained ∼83 subnetworks across the brain. At this scale, nine DMN subnetworks exhibited topographical similarity across subjects, suggesting that this approach identifies homologous neurobiological circuits across individuals. Some DMN subnetworks matched known features of brain organization corresponding with cognitive functions. Other subnetworks represented separate streams by which DMN couples with other canonical large-scale networks, including language and control networks. Together, this work provides a detailed organizational framework for studying the DMN in individual humans.
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The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients.

Issue 7 Vol 21 Published on 2020-07-01 PMID 32391912 PMCID PMC7239207
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Keywords: Troponin, Echocardiography, Myocardial injury, computed tomography, Cardiac Magnetic Resonance, Lung Ultrasound, Covid-19
DOI: https://doi.org/10.1093/ehjci/jeaa136
Authors: Bernard Cosyns In X Stijn Lochy In X Maria Luiza Luchian In X Alessia Gimelli In X Gianluca Pontone In X Sabine D Allard In X Johan de Mey In X Peter Rosseel In X Marc Dweck In X Steffen E Petersen In X Thor Edvardsen In X
Abstract: Recent EACVI recommendations described the importance of limiting cardiovascular imaging during the COVID-19 pandemic in order to reduce virus transmission, protect healthcare professionals from contamination, and reduce consumption of personal protective equipment. However, an elevated troponin remains a frequent request for cardiac imaging in COVID-19 patients, partly because it signifies cardiac injury due to a variety of causes and partly because it is known to convey a worse prognosis. The present paper aims to provide guidance to clinicians regarding the appropriateness of cardiac imaging in the context of troponin elevation and myocardial injury, how best to decipher the mechanism of myocardial injury, and how to guide patient management.
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Defining Individual-Specific Functional Neuroanatomy for Precision Psychiatry.

Issue 1 Vol 88 Published on 2020-07-01 PMID 31916942 PMCID PMC7203002
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Keywords: fMRI, reliability, Individual Differences, Functional Connectivity, Brain Networks, Precision Imaging
DOI: https://doi.org/10.1016/j.biopsych.2019.10.026
Authors: Caterina Gratton In X Brian T Kraus In X Deanna J Greene In X Evan M Gordon In X Timothy O Laumann In X Steven M Nelson In X Nico U F Dosenbach In X Steven E Petersen In X
Abstract: Studies comparing diverse groups have shown that many psychiatric diseases involve disruptions across distributed large-scale networks of the brain. There is hope that functional magnetic resonance imaging (fMRI) functional connectivity techniques will shed light on these disruptions, providing prognostic and diagnostic biomarkers as well as targets for therapeutic interventions. However, to date, progress on clinical translation of fMRI methods has been limited. Here, we argue that this limited translation is driven by a combination of intersubject heterogeneity and the relatively low reliability of standard fMRI techniques at the individual level. We review a potential solution to these limitations: the use of new "precision" fMRI approaches that shift the focus of analysis from groups to single individuals through the use of extended data acquisition strategies. We begin by discussing the potential advantages of fMRI functional connectivity methods for improving our understanding of functional neuroanatomy and disruptions in psychiatric disorders. We then discuss the budding field of precision fMRI and findings garnered from this work. We demonstrate that precision fMRI can improve the reliability of functional connectivity measures, while showing high stability and sensitivity to individual differences. We close by discussing the application of these approaches to clinical settings.
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Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy.

Open Access Issue 11 Vol 106 Published on 2020-06-01 PMID 31822572 PMCID PMC7282549
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Keywords: hypertrophic cardiomyopathy, Cardiac Magnetic Resonance (Cmr) Imaging, Advanced Cardiac Imaging
DOI: https://doi.org/10.1136/heartjnl-2019-315848
Authors: Claudia Camaioni In X Kristopher D Knott In X Joao B Augusto In X Andreas Seraphim In X Stefania Rosmini In X Fabrizio Ricci In X Redha Boubertakh In X Hui Xue In X Rebecca Hughes In X Gaby Captur In X Luis Rocha Lopes In X Louise Anne Elizabeth Brown In X Charlotte Manisty In X Steffen Erhard Petersen In X Sven Plein In X Peter Kellman In X Saidi A Mohiddin In X James C Moon In X
Abstract:

Objective

In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM.

Methods

101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE.

Results

In HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R2 for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001).

Conclusions

Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker.
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The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions.

Open Access Issue 1 Vol 11 Published on 2020-05-01 PMID 32457287 PMCID PMC7250878
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Keywords:
DOI: https://doi.org/10.1038/s41467-020-15948-9
Authors: Thomas J Littlejohns In X Jo Holliday In X Lorna M Gibson In X Steve Garratt In X Niels Oesingmann In X Fidel Alfaro-Almagro In X Jimmy D Bell In X Chris Boultwood In X Rory Collins In X Megan C Conroy In X Nicola Crabtree In X Nicola Doherty In X Alejandro F Frangi In X Nicholas C Harvey In X Paul Leeson In X Karla L Miller In X Stefan Neubauer In X Steffen E Petersen In X Jonathan Sellors In X Simon Sheard In X Stephen M Smith In X Cathie L M Sudlow In X Paul M Matthews In X Naomi E Allen In X
Abstract: UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
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Corrigendum: Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

Issue 5 Vol 30 Published on 2020-05-01 PMID 32347306 PMCID PMC7197380
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Keywords:
DOI: https://doi.org/10.1093/cercor/bhaa092
Authors: Adam T Eggebrecht In X Jed T Elison In X Eric Feczko In X Alexandre Todorov In X Jason J Wolff In X Sridhar Kandala In X Chloe M Adams In X Abraham Z Snyder In X John D Lewis In X Annette M Estes In X Lonnie Zwaigenbaum In X Kelly N Botteron In X Robert C McKinstry In X John N Constantino In X Alan Evans In X Heather C Hazlett In X Stephen Dager In X Sarah J Paterson In X Robert T Schultz In X Martin A Styner In X Guido Gerig In X Samir Das In X Penelope Kostopoulos In X In X Bradley L Schlaggar In X Steven E Petersen In X Joseph Piven In X John R Pruett In X
Abstract: No Abstract Available
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Cardiac magnetic resonance radiomics: basic principles and clinical perspectives.

Open Access Issue 4 Vol 21 Published on 2020-04-01 PMID 32142107 PMCID PMC7082724
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Keywords: Texture analysis, Machine Learning, Cardiac Magnetic Resonance, Radiomics, Image-based Diagnosis
DOI: https://doi.org/10.1093/ehjci/jeaa028
Authors: Zahra Raisi-Estabragh In X Cristian Izquierdo In X Victor M Campello In X Carlos Martin-Isla In X Akshay Jaggi In X Nicholas C Harvey In X Karim Lekadir In X Steffen E Petersen In X
Abstract: Radiomics is a novel image analysis technique, whereby voxel-level information is extracted from digital images and used to derive multiple numerical quantifiers of shape and tissue character. Cardiac magnetic resonance (CMR) is the reference imaging modality for assessment of cardiac structure and function. Conventional analysis of CMR scans is mostly reliant on qualitative image analysis and basic geometric quantifiers. Small proof-of-concept studies have demonstrated the feasibility and superior diagnostic accuracy of CMR radiomics analysis over conventional reporting. CMR radiomics has the potential to transform our approach to defining image phenotypes and, through this, improve diagnostic accuracy, treatment selection, and prognostication. The purpose of this article is to provide an overview of radiomics concepts for clinicians, with particular consideration of application to CMR. We will also review existing literature on CMR radiomics, discuss challenges, and consider directions for future work.
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The Prognostic Significance of Quantitative Myocardial Perfusion: An Artificial Intelligence-Based Approach Using Perfusion Mapping.

Open Access Issue 16 Vol 141 Published on 2020-04-01 PMID 32078380 PMCID PMC7176346
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Keywords: Myocardial perfusion, Cardiovascular Magnetic Resonance, Cardiovascular Outcomes, Inline Perfusion Quantification
DOI: https://doi.org/10.1161/circulationaha.119.044666
Authors: Kristopher D Knott In X Andreas Seraphim In X Joao B Augusto In X Hui Xue In X Liza Chacko In X Nay Aung In X Steffen E Petersen In X Jackie A Cooper In X Charlotte Manisty In X Anish N Bhuva In X Tushar Kotecha In X Christos V Bourantas In X Rhodri H Davies In X Louise A E Brown In X Sven Plein In X Marianna Fontana In X Peter Kellman In X James C Moon In X
Abstract:

Background

Myocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance perfusion permit automated measurement clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF).

Methods

A 2-center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for comorbidities and cardiovascular magnetic resonance parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (>90 day) revascularization, and death.

Results

A total of 1049 patients were included with a median follow-up of 605 (interquartile range, 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1 mL·g-1·min-1 decrease in stress MBF, the adjusted hazard ratios for death and MACE were 1.93 (95% CI, 1.08-3.48, P=0.028) and 2.14 (95% CI, 1.58-2.90, P<0.0001), respectively, even after adjusting for age and comorbidity. For each 1 U decrease in MPR, the adjusted hazard ratios for death and MACE were 2.45 (95% CI, 1.42-4.24, P=0.001) and 1.74 (95% CI, 1.36-2.22, P<0.0001), respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only.

Conclusions

In patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.
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Cardiovascular magnetic resonance imaging volume criteria for arrhythmogenic right ventricular cardiomyopathy: need for update?

Issue 14 Vol 41 Published on 2020-04-01 PMID 32031606 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/eurheartj/ehz965
Authors: Mohammed Y Khanji In X Anwar A Chahal In X Luis R Lopes In X Steffen E Petersen In X
Abstract: No Abstract Available
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Improving cardiac MRI convolutional neural network segmentation on small training datasets and dataset shift: A continuous kernel cut approach.

Issue N/A Vol 61 Published on 2020-04-01 PMID 31972427 PMCID N/A
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Keywords: Convex Optimization, Cardiac Mri Segmentation, Normalized Cuts, Continuous Max-flow
DOI: https://doi.org/10.1016/j.media.2020.101636
Authors: Fumin Guo In X Matthew Ng In X Maged Goubran In X Steffen E Petersen In X Stefan K Piechnik In X Stefan Neubauer In X Graham Wright In X
Abstract: Cardiac magnetic resonance imaging (MRI) provides a wealth of imaging biomarkers for cardiovascular disease care and segmentation of cardiac structures is required as a first step in enumerating these biomarkers. Deep convolutional neural networks (CNNs) have demonstrated remarkable success in image segmentation but typically require large training datasets and provide suboptimal results that require further improvements. Here, we developed a way to enhance cardiac MRI multi-class segmentation by combining the strengths of CNN and interpretable machine learning algorithms. We developed a continuous kernel cut segmentation algorithm by integrating normalized cuts and continuous regularization in a unified framework. The high-order formulation was solved through upper bound relaxation and a continuous max-flow algorithm in an iterative manner using CNN predictions as inputs. We applied our approach to two representative cardiac MRI datasets across a wide range of cardiovascular pathologies. We comprehensively evaluated the performance of our approach for two CNNs trained with various small numbers of training cases, tested on the same and different datasets. Experimental results showed that our approach improved baseline CNN segmentation by a large margin, reduced CNN segmentation variability substantially, and achieved excellent segmentation accuracy with minimal extra computational cost. These results suggest that our approach provides a way to enhance the applicability of CNN by enabling the use of smaller training datasets and improving the segmentation accuracy and reproducibility for cardiac MRI segmentation in research and clinical patient care.
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Prediction of Coronary Revascularization in Stable Angina: Comparison of FFRCT With CMR Stress Perfusion Imaging.

Issue 4 Vol 13 Published on 2020-04-01 PMID 31422146 PMCID N/A
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Keywords: Revascularization, Stable Angina, Cardiac Magnetic Resonance Stress Perfusion Imaging, Coronary Computed Tomography Angiography–derived Fractional Flow Reserve
DOI: https://doi.org/10.1016/j.jcmg.2019.06.028
Authors: Niels Peter Rønnow Sand In X Louise Nissen In X Simon Winther In X Steffen E Petersen In X Jelmer Westra In X Evald H Christiansen In X Pia Larsen In X Niels R Holm In X Christin Isaksen In X Grazina Urbonaviciene In X Lone Deibjerg In X Majed Husain In X Kristian K Thomsen In X Allan Rohold In X Hans Erik Bøtker In X Morten Bøttcher In X
Abstract:

Objectives

This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care-guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA.

Background

FFRCT is a novel modality for noninvasive functional testing. The clinical utility of FFRCT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown.

Methods

Prospective study of patients (n = 110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFRCT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFRCT and CMR were analyzed by core laboratories blinded for patient management.

Results

A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care-guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86% to 100%) for FFRCT versus 47% (31% to 64%) for CMR, p < 0.001; corresponding specificity was 42% (30% to 54%) versus 88% (78% to 94%), p < 0.001; negative predictive value of 97% (91% to 100%) versus 76% (67% to 85%), p < 0.05; positive predictive value of 47% (36% to 58%) versus 67% (49% to 84%), p < 0.05; and accuracy of 61% (51% to 70%) versus 74% (64% to 82%), p > 0.05, respectively.

Conclusions

In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFRCT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFRCT, whereas specificity was highest for CMR.
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Association Between Recreational Cannabis Use and Cardiac Structure and Function.

Issue 3 Vol 13 Published on 2020-03-01 PMID 31864983 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.jcmg.2019.10.012
Authors: Mohammed Y Khanji In X Magnus T Jensen In X Asmaa A Kenawy In X Zahra Raisi-Estabragh In X Jose M Paiva In X Nay Aung In X Kenneth Fung In X Elena Lukaschuk In X Filip Zemrak In X Aaron M Lee In X Ahmet Barutcu In X Edd Maclean In X Jackie Cooper In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract: No Abstract Available
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Correction of respiratory artifacts in MRI head motion estimates.

Issue N/A Vol 208 Published on 2020-03-01 PMID 31778819 PMCID PMC7307712
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DOI: https://doi.org/10.1016/j.neuroimage.2019.116400
Authors: Damien A Fair In X Oscar Miranda-Dominguez In X Abraham Z Snyder In X Anders Perrone In X Eric A Earl In X Andrew N Van In X Jonathan M Koller In X Eric Feczko In X M Dylan Tisdall In X Andre van der Kouwe In X Rachel L Klein In X Amy E Mirro In X Jacqueline M Hampton In X Babatunde Adeyemo In X Timothy O Laumann In X Caterina Gratton In X Deanna J Greene In X Bradley L Schlaggar In X Donald J Hagler In X Richard Watts In X Hugh Garavan In X Deanna M Barch In X Joel T Nigg In X Steven E Petersen In X Anders M Dale In X Sarah W Feldstein-Ewing In X Bonnie J Nagel In X Nico U F Dosenbach In X
Abstract: Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.
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Our study, 'Correction of respiratory artifacts in MRI head motion estimates.', is now published! Big congratulations to Fair and the team for making this happen:
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Comparison of quantitative flow ratio and fractional flow reserve with myocardial perfusion scintigraphy and cardiovascular magnetic resonance as reference standard. A Dan-NICAD substudy.

Open Access Issue 3 Vol 36 Published on 2020-03-01 PMID 31745744 PMCID PMC7080669
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Keywords: Myocardial ischemia, Stable Angina, Cardiovascular Magnetic Resonance, Fractional Flow Reserve, Myocardial Perfusion Scintigraphy, Quantitative Flow Ratio
DOI: https://doi.org/10.1007/s10554-019-01737-z
Authors: Martin Sejr-Hansen In X Jelmer Westra In X Simon Winther In X Shengxian Tu In X Louise Nissen In X Lars Gormsen In X Steffen E Petersen In X June Ejlersen In X Christin Isaksen In X Hans Erik Bøtker In X Morten Bøttcher In X Evald H Christiansen In X Niels Ramsing Holm In X
Abstract: Quantitative flow ratio (QFR) and fractional flow reserve (FFR) have not yet been compared head to head with perfusion imaging as reference for myocardial ischemia. We aimed to compare the diagnostic accuracy of QFR and FFR with myocardial perfusion scintigraphy (MPS) or cardiovascular magnetic resonance (CMR) as reference. This study is a predefined post hoc analysis of the Dan-NICAD study (NCT02264717). Patients with suspected coronary artery disease by coronary computed tomography angiography (CCTA) were randomized 1:1 to MPS or CMR and were referred to invasive coronary angiography with FFR and predefined QFR assessment. Paired data with FFR, QFR and MPS or CMR were available for 232 vessels with stenosis in 176 patients. Perfusion defects were detected in 57 vessel territories (25%). For QFR and FFR the diagnostic accuracy was 61% and 57% (p = 0.18) and area under the receiver operating curve was 0.64 vs. 0.58 (p = 0.22). Stenoses with absolute indication for stenting due to diameter stenosis > 90% by visual estimate were not classified as significant by either QFR or MPS/CMR in 21% (7 of 34) of cases. The diagnostic performance of QFR and FFR was similar but modest with MPS or CMR as reference. Comparable performance levels for QFR and FFR are encouraging for this pressure wire-free diagnostic method.
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Mystifying mass in the right ventricle.

Issue 3 Vol 21 Published on 2020-03-01 PMID 31584651 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jez251
Authors: S P J de Ridder In X P E Polak In X J Ter Woorst In X S E Petersen In X
Abstract: No Abstract Available
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Exceptional publication 'Mystifying mass in the right ventricle.' demonstrates innovative approaches by de Ridder:
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Fully Automated Myocardial Strain Estimation from Cardiovascular MRI-tagged Images Using a Deep Learning Framework in the UK Biobank.

Open Access Issue 1 Vol 2 Published on 2020-02-01 PMID 32715298 PMCID PMC7051160
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Keywords:
DOI: https://doi.org/10.1148/ryct.2020190032
Authors: Edward Ferdian In X Avan Suinesiaputra In X Kenneth Fung In X Nay Aung In X Elena Lukaschuk In X Ahmet Barutcu In X Edd Maclean In X Jose Paiva In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Alistair A Young In X
Abstract:

Purpose

To demonstrate the feasibility and performance of a fully automated deep learning framework to estimate myocardial strain from short-axis cardiac MRI-tagged images.

Materials and methods

In this retrospective cross-sectional study, 4508 cases from the U.K. Biobank were split randomly into 3244 training cases, 812 validation cases, and 452 test cases. Ground truth myocardial landmarks were defined and tracked by manual initialization and correction of deformable image registration using previously validated software with five readers. The fully automatic framework consisted of (a) a convolutional neural network (CNN) for localization and (b) a combination of a recurrent neural network (RNN) and a CNN to detect and track the myocardial landmarks through the image sequence for each slice. Radial and circumferential strain were then calculated from the motion of the landmarks and averaged on a slice basis.

Results

Within the test set, myocardial end-systolic circumferential Green strain errors were -0.001 ± 0.025, -0.001 ± 0.021, and 0.004 ± 0.035 in the basal, mid-, and apical slices, respectively (mean ± standard deviation of differences between predicted and manual strain). The framework reproduced significant reductions in circumferential strain in participants with diabetes, hypertensive participants, and participants with a previous heart attack. Typical processing time was approximately 260 frames (approximately 13 slices) per second on a GPU with 12 GB RAM compared with 6-8 minutes per slice for the manual analysis.

Conclusion

The fully automated combined RNN and CNN framework for analysis of myocardial strain enabled unbiased strain evaluation in a high-throughput workflow, with similar ability to distinguish impairment due to diabetes, hypertension, and previous heart attack.Published under a CC BY 4.0 license. Supplemental material is available for this article.
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Breakthrough research 'Fully Automated Myocardial Strain Estimation from Cardiovascular MRI-tagged Images Using a Deep Learning Framework in the UK Biobank.' by Ferdian & team reshapes scientific understanding:
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Human Brain Functional Network Organization Is Disrupted After Whole-Brain Radiation Therapy.

Issue 1 Vol 10 Published on 2020-02-01 PMID 31964163 PMCID PMC7044779
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Keywords: Cognition, Functional magnetic resonance imaging, Radiotherapy, Radiation dosage, Cognitive Dysfunction, Executive Function
DOI: https://doi.org/10.1089/brain.2019.0713
Authors: Timothy J Mitchell In X Benjamin A Seitzman In X Nicholas Ballard In X Steven E Petersen In X Joshua S Shimony In X Eric C Leuthardt In X
Abstract: Radiation therapy (RT) plays a vital role in the treatment of brain cancers, but it frequently results in cognitive decline in the patients who receive it. Because the underlying mechanisms for this decline remain poorly understood, the brain is typically treated as a single, uniform volume when evaluating the toxic effects of RT plans. This ignorance represents a significant deficit in the field of radiation oncology, as the technology exists to manipulate dose distributions to spare regions of the brain, but there exists no body of knowledge regarding what is critical to spare. This deficit exists due to the numerous confounding factors that are frequently associated with radiotherapy, including the tumors themselves, other treatments such as surgery and chemotherapy, and dose gradients across the brain. Here, we present a case in which a 57-year-old male patient received a uniform dose of radiation across the whole brain, did not receive concurrent chemotherapy, had minimal surgical intervention and a small tumor burden, and received resting-state functional magnetic resonance imaging (fMRI) scans both before and after RT. To our knowledge, this is the first study on the effects of whole-brain radiotherapy on functional network organization, and this patient's treatment regimen represents a rare and non-replicable opportunity to isolate the effects of radiation on functional connectivity. We observed substantial changes in the subject's behavior and functional network organization over a 12-month timeframe. Interestingly, the homogenous radiation dose to the brain had a heterogeneous effect on cortical networks, and the functional networks most affected correspond with observed cognitive behavioral deficits. This novel study suggests that the cognitive decline that occurs after whole-brain radiation therapy may be network specific and related to the disruption of large-scale distributed functional systems, and it indicates that fMRI is a promising avenue of study for optimizing cognitive outcomes after RT.
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Delighted to announce our latest publication 'Human Brain Functional Network Organization Is Disrupted After Whole-Brain Radiation Therapy.' by Mitchell et al:
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Integrative and Network-Specific Connectivity of the Basal Ganglia and Thalamus Defined in Individuals.

Issue 4 Vol 105 Published on 2020-02-01 PMID 31836321 PMCID PMC7035165
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Keywords: Resting state, Thalamus, Deep brain stimulation, Basal Ganglia, Functional Connectivity, Brain Networks, Subcortex, Precision Functional Mapping
DOI: https://doi.org/10.1016/j.neuron.2019.11.012
Authors: Deanna J Greene In X Scott Marek In X Evan M Gordon In X Joshua S Siegel In X Caterina Gratton In X Timothy O Laumann In X Adrian W Gilmore In X Jeffrey J Berg In X Annie L Nguyen In X Donna Dierker In X Andrew N Van In X Mario Ortega In X Dillan J Newbold In X Jacqueline M Hampton In X Ashley N Nielsen In X Kathleen B McDermott In X Jarod L Roland In X Scott A Norris In X Steven M Nelson In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X Nico U F Dosenbach In X
Abstract: The basal ganglia, thalamus, and cerebral cortex form an interconnected network implicated in many neurological and psychiatric illnesses. A better understanding of cortico-subcortical circuits in individuals will aid in development of personalized treatments. Using precision functional mapping-individual-specific analysis of highly sampled human participants-we investigated individual-specific functional connectivity between subcortical structures and cortical functional networks. This approach revealed distinct subcortical zones of network specificity and multi-network integration. Integration zones were systematic, with convergence of cingulo-opercular control and somatomotor networks in the ventral intermediate thalamus (motor integration zones), dorsal attention and visual networks in the pulvinar, and default mode and multiple control networks in the caudate nucleus. The motor integration zones were present in every individual and correspond to consistently successful sites of deep brain stimulation (DBS; essential tremor). Individually variable subcortical zones correspond to DBS sites with less consistent treatment effects, highlighting the importance of PFM for neurosurgery, neurology, and psychiatry.
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Chronic Obstructive Pulmonary Disease as a Predictor of Cardiovascular Risk: A Case-Control Study.

Issue 1 Vol 17 Published on 2020-02-01 PMID 31833441 PMCID N/A
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Keywords: Pulse wave velocity, Cardiovascular Risk, Surrogate Markers, Risk Prediction Models, Cardiovascular Surrogate Markers
DOI: https://doi.org/10.1080/15412555.2019.1694501
Authors: Mohammed Y Khanji In X Ian S Stone In X Redha Boubertakh In X Jackie A Cooper In X Neil C Barnes In X Steffen E Petersen In X
Abstract: Chronic obstructive pulmonary disease (COPD) is a complex multi-morbid disorder with significant cardiac mortality. Current cardiovascular risk prediction models do not include COPD. We investigated whether COPD modifies future cardiovascular risk to determine if it should be considered in risk prediction models.Case-control study using baseline data from two randomized controlled trials performed between 2012 and 2015. Of the 90 eligible subjects, 26 COPD patients with lung hyperinflation were propensity matched for 10-year global cardiovascular risk score (QRISK2) with 26 controls having normal lung function. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. Differences in pulse wave velocity (PWV), total arterial compliance (TAC) and aortic distensibility were main outcome measures.PWV (mean difference 1.0 m/s, 95% CI 0.02-1.92; p = 0.033) and TAC (mean difference -0.27 mL/m2/mmHg, 95% CI 0.39-0.15; p < 0.001) were adversely affected in COPD compared to the control group. The PWV difference equates to an age, sex and risk-factor adjusted increase in relative risk of cardiovascular events and mortality of 14% and 15%, respectively.There were no differences in aortic distensibility. In the whole cohort (n = 90) QRISK2 (β = 0.045, p = 0.005) was associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV were modified by COPD, where the interaction term reached significance (p = 0.014). FEV1 (β = 0.055 (0.027), p = 0.041) and pulse (B = -0.006 (0.002), p = 0.003) were associated with TAC in multivariate analysis.Markers of cardiovascular outcomes are adversely affected in COPD patients with lung hyperinflation compared to controls matched for global cardiovascular risk. Cardiovascular risk algorithms may benefit from the addition of a COPD variable to improve risk prediction and guide management.HAPPY London ClinicalTrials.gov: NCT01911910 and HZC116601; ClinicalTrials.gov: NCT01691885.
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EuroCMR 2019 highlights.

Issue 2 Vol 21 Published on 2020-02-01 PMID 31821461 PMCID N/A
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Keywords: Cardiomyopathy, Vascular disease, Ischaemic Heart Disease, Valvular Disease, Cardiovascular Magnetic Resonance, Arrhythmia And Congenital Heart Disease
DOI: https://doi.org/10.1093/ehjci/jez307
Authors: Jose F Rodriguez-Palomares In X Thor Edvardsen In X Ana G Almeida In X Stephen E Petersen In X
Abstract: Cardiovascular magnetic resonance (CMR) has become one of the main imaging techniques for the diagnosis and prognostic stratification of the different cardiovascular diseases. Proof of this is the growing interest in training in this imaging technique which was evident in the past EuroCMR 2019 where 1379 specialists (26.5% more than in the previous edition) met in Lido (Venice) to discuss the latest scientific advances in the CMR field. In this review, we will discuss the most recent research presented during this congress that aroused maximum interest.
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A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum.

Issue N/A Vol 206 Published on 2020-02-01 PMID 31634545 PMCID PMC6981071
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Keywords: Cerebellum, Networks, Functional Connectivity, Subcortical, Resting-state
DOI: https://doi.org/10.1016/j.neuroimage.2019.116290
Authors: Benjamin A Seitzman In X Caterina Gratton In X Scott Marek In X Ryan V Raut In X Nico U F Dosenbach In X Bradley L Schlaggar In X Steven E Petersen In X Deanna J Greene In X
Abstract: An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011, and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels.
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So excited to see our paper, 'A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum.', in print! A great team effort with Seitzman et al.:
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2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC).

Issue 5 Vol 41 Published on 2020-02-01 PMID 31504425 PMCID N/A
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Keywords: Arrhythmia, Tachycardia, Ablation, Focal, Supraventricular, Guidelines, Re-entrant, Nodal, Pre-excitation, Flutter, Atrioventricular, Junctional, Macro–re-entrant
DOI: https://doi.org/10.1093/eurheartj/ehz467
Authors: Josep Brugada In X Demosthenes G Katritsis In X Elena Arbelo In X Fernando Arribas In X Jeroen J Bax In X Carina Blomström-Lundqvist In X Hugh Calkins In X Domenico Corrado In X Spyridon G Deftereos In X Gerhard-Paul Diller In X Juan J Gomez-Doblas In X Bulent Gorenek In X Andrew Grace In X Siew Yen Ho In X Juan-Carlos Kaski In X Karl-Heinz Kuck In X Pier David Lambiase In X Frederic Sacher In X Georgia Sarquella-Brugada In X Piotr Suwalski In X Antonio Zaza In X In X
Abstract: No Abstract Available
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Breakthrough research '2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC).' by Brugada & team reshapes scientific understanding:
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Recent Trends and Potential Drivers of Non-invasive Cardiovascular Imaging Use in the United States of America and England.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33575273 PMCID PMC7870990
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Keywords: Imaging, Magnetic Resonance Imaging, Computerized tomography, Diagnostic Testing, Nuclear Cardiology And Pet
DOI: https://doi.org/10.3389/fcvm.2020.617771
Authors: Steffen E Petersen In X Rocco Friebel In X Victor Ferrari In X Yuchi Han In X Nay Aung In X Asmaa Kenawy In X Timothy S E Albert In X Huseyin Naci In X
Abstract: Background: Non-invasive Cardiovascular imaging (NICI), including cardiovascular magnetic resonance (CMR) imaging provides important information to guide the management of patients with cardiovascular conditions. Current rates of NICI use and potential policy determinants in the United States of America (US) and England remain unexplored. Methods: We compared NICI activity in the US (Medicare fee-for-service, 2011-2015) and England (National Health Service, 2012-2016). We reviewed recommendations related to CMR from Clinical Practice Guidelines, Appropriate Use Criteria (AUC), and Choosing Wisely. We then categorized recommendations according to whether CMR was the only recommended NICI technique (substitutable indications). Reimbursement policies in both settings were systematically collated and reviewed using publicly available information. Results: The 2015 rate of NICI activity in the US was 3.1 times higher than in England (31,055 vs. 9,916 per 100,000 beneficiaries). The proportion of CMR of all NICI was small in both jurisdictions, but nuclear cardiac imaging was more frequent in the US in absolute and relative terms. American and European CPGs were similar, both in terms of number of recommendations and proportions of indications where CMR was not the only recommended NICI technique (substitutable indications). Reimbursement schemes for NICI activity differed for physicians and hospitals between the two settings. Conclusions: Fee-for-service physician compensation in the US for NICI may contribute to higher NICI activity compared to England where physicians are salaried. Reimbursement arrangements for the performance of the test may contribute to the higher proportion of nuclear cardiac imaging out of the total NICI activity. Differences in CPG recommendations appear not to explain the variation in NICI activity between the US and England.
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Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.

Open Access Issue N/A Vol 5 Published on 2020-01-01 PMID 33537459 PMCID PMC7836029
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Keywords: Pandemic, Healthcare Workers, Covid-19
DOI: https://doi.org/10.12688/wellcomeopenres.16051.2
Authors: João B Augusto In X Katia Menacho In X Mervyn Andiapen In X Ruth Bowles In X Maudrian Burton In X Sophie Welch In X Anish N Bhuva In X Andreas Seraphim In X Corinna Pade In X George Joy In X Melanie Jensen In X Rhodri H Davies In X Gabriella Captur In X Marianna Fontana In X Hugh Montgomery In X Ben O'Brien In X Aroon D Hingorani In X Teresa Cutino-Moguel In X Áine McKnight In X Hakam Abbass In X Mashael Alfarih In X Zoe Alldis In X Georgina L Baca In X Alex Boulter In X Olivia V Bracken In X Natalie Bullock In X Nicola Champion In X Carmen Chan In X Xose Couto-Parada In X Keenan Dieobi-Anene In X Karen Feehan In X Gemma Figtree In X Melanie C Figtree In X Malcolm Finlay In X Nasim Forooghi In X Joseph M Gibbons In X Peter Griffiths In X Matt Hamblin In X Lee Howes In X Ivie Itua In X Meleri Jones In X Victor Jardim In X Vikas Kapil In X Wing-Yiu Jason Lee In X Vineela Mandadapu In X Celina Mfuko In X Oliver Mitchelmore In X Susana Palma In X Kush Patel In X Steffen E Petersen In X Brian Piniera In X Rosalind Raine In X Alicja Rapala In X Amy Richards In X Genine Sambile In X Jorge Couto de Sousa In X Michelle Sugimoto In X George D Thornton In X Jessica Artico In X Dan Zahedi In X Ruth Parker In X Mathew Robathan In X Lauren M Hickling In X Ntobeko Ntusi In X Amanda Semper In X Tim Brooks In X Jessica Jones In X Art Tucker In X Jessry Veerapen In X Mohit Vijayakumar In X Theresa Wodehouse In X Lucinda Wynne In X Thomas A Treibel In X Mahdad Noursadeghi In X Charlotte Manisty In X James C Moon In X
Abstract: Background: Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods: We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results: Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions: This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/.
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Our new article, 'Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.', is finally out! Big thanks to Augusto and the coauthors for their dedication & insights:
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Repeatability of Cardiac Magnetic Resonance Radiomics: A Multi-Centre Multi-Vendor Test-Retest Study.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33344517 PMCID PMC7738466
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Keywords: Reproducibility, Repeatability, Texture analysis, Cardiovascular Magnetic Resonance, Test-retest, Radiomics
DOI: https://doi.org/10.3389/fcvm.2020.586236
Authors: Zahra Raisi-Estabragh In X Polyxeni Gkontra In X Akshay Jaggi In X Jackie Cooper In X João Augusto In X Anish N Bhuva In X Rhodri H Davies In X Charlotte H Manisty In X James C Moon In X Patricia B Munroe In X Nicholas C Harvey In X Karim Lekadir In X Steffen E Petersen In X
Abstract: Aims: To evaluate the repeatability of cardiac magnetic resonance (CMR) radiomics features on test-retest scanning using a multi-centre multi-vendor dataset with a varied case-mix. Methods and Results: The sample included 54 test-retest studies from the VOLUMES resource (thevolumesresource.com). Images were segmented according to a pre-defined protocol to select three regions of interest (ROI) in end-diastole and end-systole: right ventricle, left ventricle (LV), and LV myocardium. We extracted radiomics shape features from all three ROIs and, additionally, first-order and texture features from the LV myocardium. Overall, 280 features were derived per study. For each feature, we calculated intra-class correlation coefficient (ICC), within-subject coefficient of variation, and mean relative difference. We ranked robustness of features according to mean ICC stratified by feature category, ROI, and cardiac phase, demonstrating a wide range of repeatability. There were features with good and excellent repeatability (ICC ≥ 0.75) within all feature categories and ROIs. A high proportion of first-order and texture features had excellent repeatability (ICC ≥ 0.90), however, these categories also contained features with the poorest repeatability (ICC < 0.50). Conclusion: CMR radiomic features have a wide range of repeatability. This paper is intended as a reference for future researchers to guide selection of the most robust features for clinical CMR radiomics models. Further work in larger and richer datasets is needed to further define the technical performance and clinical utility of CMR radiomics.
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Pathological Cluster Identification by Unsupervised Analysis in 3,822 UK Biobank Cardiac MRIs.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33313075 PMCID PMC7701336
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Keywords: Cluster analysis, Feature extraction, Uk Biobank, Cine Mri, Cardiac Pathology
DOI: https://doi.org/10.3389/fcvm.2020.539788
Authors: Qiao Zheng In X Hervé Delingette In X Kenneth Fung In X Steffen E Petersen In X Nicholas Ayache In X
Abstract: We perform unsupervised analysis of image-derived shape and motion features extracted from 3,822 cardiac Magnetic resonance imaging (MRIs) of the UK Biobank. First, with a feature extraction method previously published based on deep learning models, we extract from each case 9 feature values characterizing both the cardiac shape and motion. Second, a feature selection is performed to remove highly correlated feature pairs. Third, clustering is carried out using a Gaussian mixture model on the selected features. After analysis, we identify 2 small clusters that probably correspond to 2 pathological categories. Further confirmation using a trained classification model and dimensionality reduction tools is carried out to support this finding. Moreover, we examine the differences between the other large clusters and compare our measures with the ground truth.
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Thrilled to see our study, 'Pathological Cluster Identification by Unsupervised Analysis in 3,822 UK Biobank Cardiac MRIs.', now published! Kudos to Zheng and the entire team for their hard work:
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Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study.

Open Access Issue N/A Vol 11 Published on 2020-01-01 PMID 33262790 PMCID PMC7686798
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Keywords: Obesity, Lipid profile, Mendelian Randomization, Covid-19, Sars-cov-2
DOI: https://doi.org/10.3389/fgene.2020.586308
Authors: Nay Aung In X Mohammed Y Khanji In X Patricia B Munroe In X Steffen E Petersen In X
Abstract:

Background

Cross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present.

Methods

We conducted multivariable logistic regression to evaluate the observational associations between obesity traits (body mass index [BMI], waist circumference [WC]), quantitative cardiometabolic parameters (systolic blood pressure [SBP], serum glucose, serum glycated hemoglobin [HbA1c], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and SARS-CoV-2 positivity in the UK Biobank cohort. One-sample MR was performed by using the genetic risk scores of obesity and cardiometabolic traits constructed from independent datasets and the genotype and phenotype data from the UK Biobank. Two-sample MR was performed using the summary statistics from COVID-19 host genetics initiative. Cox proportional hazard models were fitted to assess the risk conferred by different genetic quintiles of causative exposure traits.

Results

The study comprised 1,211 European participants who were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 387,079 participants who were either untested or tested negative between 16 March 2020 to 31 May 2020. Observationally, higher BMI, WC, HbA1c and lower HDL-cholesterol were associated with higher odds of COVID-19 infection. One-sample MR analyses found causal associations between higher genetically determined BMI and LDL cholesterol and increased risk of COVID-19 (odds ratio [OR]: 1.15, confidence interval [CI]: 1.05-1.26 and OR: 1.58, CI: 1.21-2.06, per 1 standard deviation increment in BMI and LDL cholesterol respectively). Two-sample MR produced concordant results. Cox models indicated that individuals in the higher genetic risk score quintiles of BMI and LDL were more predisposed to COVID-19 (hazard ratio [HR]: 1.24, CI: 1.03-1.49 and HR: 1.37, CI: 1.14-1.65, for the top vs the bottom quintile for BMI and LDL cholesterol, respectively).

Conclusion

We identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment.
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Radiomics Signatures of Cardiovascular Risk Factors in Cardiac MRI: Results From the UK Biobank.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33240940 PMCID PMC7667130
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Keywords: Cardiovascular risk factors, Machine Learning, Cardiovascular Magnetic Resonance, Uk Biobank, Radiomics
DOI: https://doi.org/10.3389/fcvm.2020.591368
Authors: Irem Cetin In X Zahra Raisi-Estabragh In X Steffen E Petersen In X Sandy Napel In X Stefan K Piechnik In X Stefan Neubauer In X Miguel A Gonzalez Ballester In X Oscar Camara In X Karim Lekadir In X
Abstract: Cardiovascular magnetic resonance (CMR) radiomics is a novel technique for advanced cardiac image phenotyping by analyzing multiple quantifiers of shape and tissue texture. In this paper, we assess, in the largest sample published to date, the performance of CMR radiomics models for identifying changes in cardiac structure and tissue texture due to cardiovascular risk factors. We evaluated five risk factor groups from the first 5,065 UK Biobank participants: hypertension (n = 1,394), diabetes (n = 243), high cholesterol (n = 779), current smoker (n = 320), and previous smoker (n = 1,394). Each group was randomly matched with an equal number of healthy comparators (without known cardiovascular disease or risk factors). Radiomics analysis was applied to short axis images of the left and right ventricles at end-diastole and end-systole, yielding a total of 684 features per study. Sequential forward feature selection in combination with machine learning (ML) algorithms (support vector machine, random forest, and logistic regression) were used to build radiomics signatures for each specific risk group. We evaluated the degree of separation achieved by the identified radiomics signatures using area under curve (AUC), receiver operating characteristic (ROC), and statistical testing. Logistic regression with L1-regularization was the optimal ML model. Compared to conventional imaging indices, radiomics signatures improved the discrimination of risk factor vs. healthy subgroups as assessed by AUC [diabetes: 0.80 vs. 0.70, hypertension: 0.72 vs. 0.69, high cholesterol: 0.71 vs. 0.65, current smoker: 0.68 vs. 0.65, previous smoker: 0.63 vs. 0.60]. Furthermore, we considered clinical interpretation of risk-specific radiomics signatures. For hypertensive individuals and previous smokers, the surface area to volume ratio was smaller in the risk factor vs. healthy subjects; perhaps reflecting a pattern of global concentric hypertrophy in these conditions. In the diabetes subgroup, the most discriminatory radiomics feature was the median intensity of the myocardium at end-systole, which suggests a global alteration at the myocardial tissue level. This study confirms the feasibility and potential of CMR radiomics for deeper image phenotyping of cardiovascular health and disease. We demonstrate such analysis may have utility beyond conventional CMR metrics for improved detection and understanding of the early effects of cardiovascular risk factors on cardiac structure and tissue.
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Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33195445 PMCID PMC7536335
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Keywords: Mortality, Cardiomyopathy, Cardiac Magnetic Resonance, Left Ventricular Non-compaction, Left Ventricular Trabeculation
DOI: https://doi.org/10.3389/fcvm.2020.00158
Authors: Filip Zemrak In X Zahra Raisi-Estabragh In X Mohammed Y Khanji In X Saidi A Mohiddin In X Oliver Bruder In X Anja Wagner In X Massimo Lombardi In X Juerg Schwitter In X Albert C van Rossum In X Günter Pilz In X Detlev Nothnagel In X Henning Steen In X Eike Nagel In X Sanjay K Prasad In X Christina C Deluigi In X Thorsten Dill In X Herbert Frank In X Steffen Schneider In X Heiko Mahrholdt In X Steffen E Petersen In X
Abstract: Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry. Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3. Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.
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COVID-19 and the UK Biobank-Opportunities and Challenges for Research and Collaboration With Other Large Population Studies.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 33195444 PMCID PMC7481380
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Keywords: epidemiology, Population Studies, Precision Medicine, Uk Biobank, Covid-19
DOI: https://doi.org/10.3389/fcvm.2020.00156
Authors: Mohammed Y Khanji In X Nay Aung In X C Anwar A Chahal In X Steffen E Petersen In X
Abstract: Large population studies such as the UK Biobank provide great opportunities for understanding the pathophysiology, health impact and prognostic factors associated with COVID-19, a condition that has had significant impact on almost everyone around the world. We highlight the vast opportunities, challenges and limitations for research and collaboration from the UK Biobank and other large population studies in helping us better understand and manage both current and potential future pandemics.
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Editorial: Current and Future Role of Artificial Intelligence in Cardiac Imaging.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 32850987 PMCID PMC7426695
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Keywords: Artificial intelligence, Big Data, Cardiac Image Analysis, Ai Adoption And Translation, Cardiac Imaging Modalities, Cardiovascular Personalized Medicine
DOI: https://doi.org/10.3389/fcvm.2020.00137
Authors: Karim Lekadir In X Tim Leiner In X Alistair A Young In X Steffen E Petersen In X
Abstract: No Abstract Available
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Renin-Angiotensin-Aldosterone System Blockers Are Not Associated With Coronavirus Disease 2019 (COVID-19) Hospitalization: Study of 1,439 UK Biobank Cases.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 32766285 PMCID PMC7381180
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Keywords: Sex, Obesity, Angiotensin converting enzyme inhibitors, Ethnicity, Angiotensin Receptor Blockers, Uk Biobank, Cardiometabolic Disease, Coronavirus Disease 2019
DOI: https://doi.org/10.3389/fcvm.2020.00138
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Maddalena Ardissino In X Mae S Bethell In X Jackie Cooper In X Cyrus Cooper In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract: Background: Cardiometabolic morbidity and medications, specifically Angiotensin Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs), have been linked with adverse outcomes from coronavirus disease 2019 (COVID-19). This study aims to investigate, factors associated with COVID-19 positivity in hospital for 1,436 UK Biobank participants; compared with individuals who tested negative, and with the untested, presumed negative, rest of the cohort. Methods: We studied 7,099 participants from the UK Biobank who had been tested for COVID-19 in hospital. We considered the following exposures: age, sex, ethnicity, body mass index (BMI), diabetes, hypertension, hypercholesterolaemia, ACEi/ARB use, prior myocardial infarction (MI), and smoking. We undertook comparisons between (1) COVID-19 positive and COVID-19 negative tested participants; and (2) COVID-19 tested positive and the remaining participants (tested negative plus untested, n = 494,838). Logistic regression models were used to investigate univariate and mutually adjusted associations. Results: Among participants tested for COVID-19, Black, Asian, and Minority ethnic (BAME) ethnicity, male sex, and higher BMI were independently associated with a positive result. BAME ethnicity, male sex, greater BMI, diabetes, hypertension, and smoking were independently associated with COVID-19 positivity compared to the remaining cohort (test negatives plus untested). However, similar associations were observed when comparing those who tested negative for COVID-19 with the untested cohort; suggesting that these factors associate with general hospitalization rather than specifically with COVID-19. Conclusions: Among participants tested for COVID-19 with presumed moderate to severe symptoms in a hospital setting, BAME ethnicity, male sex, and higher BMI are associated with a positive result. Other cardiometabolic morbidities confer increased risk of hospitalization, without specificity for COVID-19. ACE/ARB use did not associate with COVID-19 status.
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Improving the Generalizability of Convolutional Neural Network-Based Segmentation on CMR Images.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 32714943 PMCID PMC7344224
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Keywords: Artificial intelligence, Neural network, Deep Learning, Model Generalization, Cardiac Image Analysis, Cardiac Mr Image Segmentation
DOI: https://doi.org/10.3389/fcvm.2020.00105
Authors: Chen Chen In X Wenjia Bai In X Rhodri H Davies In X Anish N Bhuva In X Charlotte H Manisty In X Joao B Augusto In X James C Moon In X Nay Aung In X Aaron M Lee In X Mihir M Sanghvi In X Kenneth Fung In X Jose Miguel Paiva In X Steffen E Petersen In X Elena Lukaschuk In X Stefan K Piechnik In X Stefan Neubauer In X Daniel Rueckert In X
Abstract: Background: Convolutional neural network (CNN) based segmentation methods provide an efficient and automated way for clinicians to assess the structure and function of the heart in cardiac MR images. While CNNs can generally perform the segmentation tasks with high accuracy when training and test images come from the same domain (e.g., same scanner or site), their performance often degrades dramatically on images from different scanners or clinical sites. Methods: We propose a simple yet effective way for improving the network generalization ability by carefully designing data normalization and augmentation strategies to accommodate common scenarios in multi-site, multi-scanner clinical imaging data sets. We demonstrate that a neural network trained on a single-site single-scanner dataset from the UK Biobank can be successfully applied to segmenting cardiac MR images across different sites and different scanners without substantial loss of accuracy. Specifically, the method was trained on a large set of 3,975 subjects from the UK Biobank. It was then directly tested on 600 different subjects from the UK Biobank for intra-domain testing and two other sets for cross-domain testing: the ACDC dataset (100 subjects, 1 site, 2 scanners) and the BSCMR-AS dataset (599 subjects, 6 sites, 9 scanners). Results: The proposed method produces promising segmentation results on the UK Biobank test set which are comparable to previously reported values in the literature, while also performing well on cross-domain test sets, achieving a mean Dice metric of 0.90 for the left ventricle, 0.81 for the myocardium, and 0.82 for the right ventricle on the ACDC dataset; and 0.89 for the left ventricle, 0.83 for the myocardium on the BSCMR-AS dataset. Conclusions: The proposed method offers a potential solution to improve CNN-based model generalizability for the cross-scanner and cross-site cardiac MR image segmentation task.
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Age, sex and disease-specific associations between resting heart rate and cardiovascular mortality in the UK BIOBANK.

Open Access Issue 5 Vol 15 Published on 2020-01-01 PMID 32470091 PMCID PMC7259773
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0233898
Authors: Zahra Raisi-Estabragh In X Jackie Cooper In X Rebekah Judge In X Mohammed Y Khanji In X Patricia B Munroe In X Cyrus Cooper In X Nicholas C Harvey In X Steffen E Petersen In X
Abstract:

Objective

To define the sex, age, and disease-specific associations of resting heart rate (RHR) with cardiovascular and mortality outcomes in 502,534 individuals from the UK Biobank over 7-12 years of prospective follow-up.

Methods

The main outcomes were all-cause, cardiovascular, and ischaemic heart disease mortality. Additional outcomes included incident acute myocardial infarction (AMI), fatal AMI, and cancer mortality. We considered a wide range of confounders and the effects of competing hazards. Results are reported as hazard ratios (HR) for all-cause mortality and sub-distribution hazard ratios (SHR) for other outcomes with corresponding 95% confidence intervals (CI) per 10bpm increment of RHR.

Results

In men, for every 10bpm increase of RHR there was 22% (HR 1.22, CI 1.20 to 1.24, p = 3×10-123) greater hazard of all-cause and 17% (SHR 1.17, CI 1.13 to 1.21, p = 5.6×10-18) greater hazard of cardiovascular mortality; for women, corresponding figures were 19% (HR 1.19, CI 1.16 to 1.22, p = 8.9×10-45) and 14% (SHR 1.14, CI 1.07 to 1.22, p = 0.00008). Associations between RHR and ischaemic outcomes were of greater magnitude amongst men than women, but with similar magnitude of association for non-cardiovascular cancer mortality [men (SHR 1.18, CI 1.15-1.21, p = 5.2×10-46); women 15% (SHR 1.15, CI 1.11-1.18, p = 3.1×10-18)]. Associations with all-cause, incident AMI, and cancer mortality were of greater magnitude at younger than older ages.

Conclusions

RHR is an independent predictor of mortality, with variation by sex, age, and disease. Ischaemic disease appeared a more important driver of this relationship in men, and associations were more pronounced at younger ages.
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The Role of Multimodality Cardiovascular Imaging in Peripartum Cardiomyopathy.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 32133371 PMCID PMC7041418
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Keywords: Pregnancy, Echocardiography, Peripartum cardiomyopathy, Heart Failure, Cardiac Magnetic Resonance, Tissue Characterization
DOI: https://doi.org/10.3389/fcvm.2020.00004
Authors: Fabrizio Ricci In X Carlo De Innocentiis In X Elvira Verrengia In X Laura Ceriello In X Cesare Mantini In X Carla Pietrangelo In X Flaviano Irsuti In X Stefano Gabriele In X Alberto D'Alleva In X Mohammed Y Khanji In X Nay Aung In X Giulia Renda In X Matteo Cameli In X Steffen E Petersen In X Ernesto Di Cesare In X Sabina Gallina In X
Abstract: The burden of pregnancy-related heart disease has dramatically increased over the last decades due to the increasing age at first pregnancy and higher prevalence of cardiovascular risk factors such as diabetes, hypertension, and obesity. Pregnancy is associated with physiological changes in the cardiovascular system, including hemodynamic, metabolic, and hormonal adaptations to meet the increased metabolic demands of the mother and fetus. It has been postulated that pregnancy may act as a cardiovascular stress test to identify women at high risk for heart disease, where the inability to adequately adapt to the physiologic stress of pregnancy may reveal the presence of genetic susceptibility to cardiovascular disease or accelerate the phenotypic expression of both inherited and acquired heart diseases, such as peripartum cardiomyopathy (PPCM). PPCM is a rare and incompletely understood clinical condition. Despite recent advances in the understanding of its pathogenesis, PPCM is not attributable to a well-defined pathological mechanism, and therefore, its diagnosis still relies on the exclusion of overlapping dilated phenotypes. Cardiac imaging plays a key role in any peripartum woman with signs and symptoms of heart failure in establishing the diagnosis, ruling out life-threatening complications, guiding therapy and conveying prognostic information. Echocardiography represents the first-line imaging technique, given its robust diagnostic yield and its favorable cost-effectiveness. Cardiovascular magnetic resonance is a biologically safe high-throughput modality that allows accurate morpho-functional assessment of the cardiovascular system in addition to the unique asset of myocardial tissue characterization as a pivotal piece of information in the pathophysiological puzzle of PPCM. In this review, we will highlight current evidence on the role of multimodality imaging in the differential diagnosis, prognostic assessment, and understanding of the pathophysiological basis of PPCM.
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Image-Based Cardiac Diagnosis With Machine Learning: A Review.

Open Access Issue N/A Vol 7 Published on 2020-01-01 PMID 32039241 PMCID PMC6992607
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Keywords: Artificial intelligence, Cardiovascular disease, Machine Learning, Cardiac Imaging, Deep Learning, Automated Diagnosis, Radiomics
DOI: https://doi.org/10.3389/fcvm.2020.00001
Authors: Carlos Martin-Isla In X Victor M Campello In X Cristian Izquierdo In X Zahra Raisi-Estabragh In X Bettina Baeßler In X Steffen E Petersen In X Karim Lekadir In X
Abstract: Cardiac imaging plays an important role in the diagnosis of cardiovascular disease (CVD). Until now, its role has been limited to visual and quantitative assessment of cardiac structure and function. However, with the advent of big data and machine learning, new opportunities are emerging to build artificial intelligence tools that will directly assist the clinician in the diagnosis of CVDs. This paper presents a thorough review of recent works in this field and provide the reader with a detailed presentation of the machine learning methods that can be further exploited to enable more automated, precise and early diagnosis of most CVDs.
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Prognostic Significance of Left Ventricular Noncompaction: Systematic Review and Meta-Analysis of Observational Studies.

Open Access Issue 1 Vol 13 Published on 2020-01-01 PMID 31959004 PMCID PMC7012350
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Keywords: Prognosis, Meta-analysis, Cardiomyopathies, Cardiac Imaging Techniques
DOI: https://doi.org/10.1161/circimaging.119.009712
Authors: Nay Aung In X Sara Doimo In X Fabrizio Ricci In X Mihir M Sanghvi In X Cesar Pedrosa In X Simon P Woodbridge In X Amer Al-Balah In X Filip Zemrak In X Mohammed Y Khanji In X Patricia B Munroe In X Huseyin Naci In X Steffen E Petersen In X
Abstract:

Background

Although left ventricular noncompaction (LVNC) has been associated with an increased risk of adverse cardiovascular events, the accurate incidence of cardiovascular morbidity and mortality is unknown. We, therefore, aimed to assess the incidence rate of LVNC-related cardiovascular events.

Methods

We systematically searched observational studies reporting the adverse outcomes related to LVNC. The primary end point was cardiovascular mortality.

Results

We identified 28 eligible studies enrolling 2501 LVNC patients (mean age, 46 years; male/female ratio, 1.7). After a median follow-up of 2.9 years, the pooled event rate for cardiovascular mortality was 1.92 (95% CI, 1.54-2.30) per 100 person-years. LVNC patients had a similar risk of cardiovascular mortality compared with a dilated cardiomyopathy control group (odds ratio, 1.10 [95% CI, 0.18-6.67]). The incidence rates of all-cause mortality, stroke and systemic emboli, heart failure admission, cardiac transplantation, ventricular arrhythmias, and cardiac device implantation were 2.16, 1.54, 3.53, 1.24, 2.17, and 2.66, respectively, per 100 person-years. Meta-regression and subgroup analyses revealed that left ventricular ejection fraction, not the extent of left ventricular trabeculation, had an important influence on the variability of incidence rates. The risks of thromboembolism and ventricular arrhythmias in LVNC patients were similar to dilated cardiomyopathy patients. However, LVNC patients had a higher incidence of heart failure hospitalization than dilated cardiomyopathy patients.

Conclusions

Patients with LVNC carry a similar cardiovascular risk when compared with dilated cardiomyopathy patients. Left ventricular ejection fraction-a conventional indicator of heart failure severity, not the extent of trabeculation-appears to be an important determinant of adverse outcomes in LVNC patients. Registration: https://www.crd.york.ac.uk/PROSPERO/ Unique identifier: CRD42018096313.
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European Society of Cardiology: Cardiovascular Disease Statistics 2019 (Executive Summary).

Issue 1 Vol 6 Published on 2020-01-01 PMID 31957796 PMCID N/A
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Keywords: Mortality, Morbidity, Statistics, Cardiovascular disease, risk factors, Service Provision, European Society Of Cardiology, Health Infrastructure
DOI: https://doi.org/10.1093/ehjqcco/qcz065
Authors: In X In X In X Adam Timmis In X N Townsend In X C P Gale In X A Torbica In X M Lettino In X S E Petersen In X E A Mossialos In X A P Maggioni In X D Kazakiewicz In X H T May In X D De Smedt In X M Flather In X L Zuhlke In X J F Beltrame In X R Huculeci In X L Tavazzi In X G Hindricks In X J Bax In X B Casadei In X S Achenbach In X L Wright In X P Vardas In X
Abstract: No Abstract Available
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European Society of Cardiology: Cardiovascular Disease Statistics 2019.

Issue 1 Vol 41 Published on 2020-01-01 PMID 31820000 PMCID N/A
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Keywords: Mortality, Morbidity, Statistics, Cardiovascular disease, risk factors, Service Provision, European Society Of Cardiology, Health Infrastructure
DOI: https://doi.org/10.1093/eurheartj/ehz859
Authors: Adam Timmis In X Nick Townsend In X Chris P Gale In X Aleksandra Torbica In X Maddalena Lettino In X Steffen E Petersen In X Elias A Mossialos In X Aldo P Maggioni In X Dzianis Kazakiewicz In X Heidi T May In X Delphine De Smedt In X Marcus Flather In X Liesl Zuhlke In X John F Beltrame In X Radu Huculeci In X Luigi Tavazzi In X Gerhard Hindricks In X Jeroen Bax In X Barbara Casadei In X Stephan Achenbach In X Lucy Wright In X Panos Vardas In X In X
Abstract:

Aims

The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets.

Methods and results

In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5-23.1%] vs. 15.7% (IQR 14.5-21.1%)}, diabetes [7.7% (IQR 7.1-10.1%) vs. 5.6% (IQR 4.8-7.0%)], and among males smoking [43.8% (IQR 37.4-48.0%) vs. 26.0% (IQR 20.9-31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0-10.8) vs. 16.7% (IQR 13.9-19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655-8115)] compared with high-income [2235 (IQR 1896-3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures.

Conclusion

A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest.
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Cardiovascular research highlights from the UK Biobank: opportunities and challenges.

Issue 1 Vol 116 Published on 2020-01-01 PMID 31778147 PMCID N/A
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Keywords: Cardiovascular disease, epidemiology, Big Data, Uk Biobank
DOI: https://doi.org/10.1093/cvr/cvz294
Authors: Zahra Raisi-Estabragh In X Steffen E Petersen In X
Abstract: No Abstract Available
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2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).

Issue 4 Vol 41 Published on 2020-01-01 PMID 31504429 PMCID N/A
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Keywords: Pregnancy, Shock, Diagnosis, Thrombolysis, Anticoagulation, Treatment, Biomarkers, Echocardiography, Pulmonary embolism, Venous thrombosis, Heart Failure, risk assessment, Dyspnoea, Embolectomy, Guidelines, Venous Thromboembolism, Right Ventricle
DOI: https://doi.org/10.1093/eurheartj/ehz405
Authors: Stavros V Konstantinides In X Guy Meyer In X Cecilia Becattini In X Héctor Bueno In X Geert-Jan Geersing In X Veli-Pekka Harjola In X Menno V Huisman In X Marc Humbert In X Catriona Sian Jennings In X David Jiménez In X Nils Kucher In X Irene Marthe Lang In X Mareike Lankeit In X Roberto Lorusso In X Lucia Mazzolai In X Nicolas Meneveau In X Fionnuala Ní Áinle In X Paolo Prandoni In X Piotr Pruszczyk In X Marc Righini In X Adam Torbicki In X Eric Van Belle In X José Luis Zamorano In X In X
Abstract: No Abstract Available
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2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.

Issue 2 Vol 41 Published on 2020-01-01 PMID 31497854 PMCID N/A
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Keywords: Diabetes mellitus, Cardiovascular diseases, Prevention, Revascularization, Impaired glucose tolerance, epidemiology, risk factors, Guidelines, Patient Management, Patient-centred Care, Cardiovascular Risk Assessment, Pharmacological Treatment
DOI: https://doi.org/10.1093/eurheartj/ehz486
Authors: Francesco Cosentino In X Peter J Grant In X Victor Aboyans In X Clifford J Bailey In X Antonio Ceriello In X Victoria Delgado In X Massimo Federici In X Gerasimos Filippatos In X Diederick E Grobbee In X Tina Birgitte Hansen In X Heikki V Huikuri In X Isabelle Johansson In X Peter Jüni In X Maddalena Lettino In X Nikolaus Marx In X Linda G Mellbin In X Carl J Östgren In X Bianca Rocca In X Marco Roffi In X Naveed Sattar In X Petar M Seferović In X Miguel Sousa-Uva In X Paul Valensi In X David C Wheeler In X In X
Abstract: No Abstract Available
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Atypical Functional Connectivity in Tourette Syndrome Differs Between Children and Adults.

Issue 2 Vol 87 Published on 2020-01-01 PMID 31472979 PMCID PMC6925331
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Keywords: Development, Classification, fMRI, Tourette syndrome, Machine Learning, Functional Connectivity
DOI: https://doi.org/10.1016/j.biopsych.2019.06.021
Authors: Ashley N Nielsen In X Caterina Gratton In X Jessica A Church In X Nico U F Dosenbach In X Kevin J Black In X Steven E Petersen In X Bradley L Schlaggar In X Deanna J Greene In X
Abstract:

Background

Tourette syndrome (TS) is a neuropsychiatric disorder with symptomatology that typically changes over development. Whether and how brain function in TS also differs across development has been largely understudied. Here, we used functional connectivity magnetic resonance imaging to examine whole-brain functional networks in children and adults with TS.

Methods

Multivariate classification methods were used to find patterns among functional connections that distinguish individuals with TS from control subjects separately for children and adults (N = 202). We tested whether the patterns of connections that classify diagnosis in one age group (e.g., children) could classify diagnosis in another age group (e.g., adults). We also tested whether the developmental trajectory of these connections was altered in TS.

Results

Diagnostic classification was successful in children and adults separately but expressly did not generalize across age groups, suggesting that the patterns of functional connections that best distinguished individuals with TS from control subjects were age specific. Developmental patterns among these functional connections used for diagnostic classification deviated from typical development. Brain networks in childhood TS appeared "older" and brain networks in adulthood TS appeared "younger" in comparison with typically developing individuals.

Conclusions

Our results demonstrate that brain networks are differentially altered in children and adults with TS. The observed developmental trajectory of affected connections is consistent with theories of accelerated and/or delayed maturation, but may also involve anomalous developmental pathways. These findings further our understanding of neurodevelopmental trajectories in TS and carry implications for future applications aimed at predicting the clinical course of TS in individuals over development.
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Validation of Cardiovascular Magnetic Resonance-Derived Equation for Predicted Left Ventricular Mass Using the UK Biobank Imaging Cohort: Tool for Donor-Recipient Size Matching.

Open Access Issue 12 Vol 12 Published on 2019-12-01 PMID 31805784 PMCID PMC6922072
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Keywords: Body weight, Cardiovascular diseases, Heart transplantation, United Kingdom, Hospital
DOI: https://doi.org/10.1161/circheartfailure.119.006362
Authors: Kenneth Fung In X Caitlin Cheshire In X Jackie A Cooper In X Pedro Catarino In X Stefan K Piechnik In X Stefan Neubauer In X Sai Bhagra In X Stephen Pettit In X Steffen E Petersen In X
Abstract:

Background

Current guidance from International Society for Heart and Lung Transplantation recommends using body weight for donor-recipient size matching for heart transplantation. However, recent studies have shown that predicted heart mass, using body weight, height, age, and sex, may represent a better method of size matching. We aim to validate a cardiovascular magnetic resonance (CMR)-derived equation for predicted left ventricular mass (LVM) in a cohort of normal individuals in the United Kingdom.

Methods

This observational study was conducted in 5065 middle-aged (44-77 years old) UK Biobank participants who underwent CMR imaging in 2014 to 2015. Individuals with cancer diagnosis in the previous 12 months or history of cardiovascular disease were excluded. Predicted LVM was calculated based on participants' sex, height, and weight recorded at the time of imaging. Correlation analyses were performed between the predicted LVM and the LVM obtained from manual contouring of CMR cine images. The analysis included 3398 participants (age 61.5±7.5 years, 47.8% males).

Results

Predicted LVM was considerably higher than CMR-derived LVM (mean±SD of 138.8±28.9 g versus 86.3±20.9 g). However, there was a strong correlation between the 2 measurements (Spearman correlation coefficient 0.802, P<0.0001).

Conclusions

Predicted LVM calculated using a CMR-derived equation that incorporates height, weight, and sex has a strong correlation with CMR LVM in large cohort of normal individuals in the United Kingdom. Our findings suggest that predicted heart mass equations may be a valid tool for donor-recipient size matching for heart transplantation in the United Kingdom.
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European Association of Cardiovascular Imaging expert consensus paper: a comprehensive review of cardiovascular magnetic resonance normal values of cardiac chamber size and aortic root in adults and recommendations for grading severity.

Issue 12 Vol 20 Published on 2019-12-01 PMID 31544926 PMCID N/A
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Keywords: Grading, Severity, Cardiovascular Magnetic Resonance, Position Statement, Cardiac Chambers
DOI: https://doi.org/10.1093/ehjci/jez232
Authors: Steffen E Petersen In X Mohammed Y Khanji In X Sven Plein In X Patrizio Lancellotti In X Chiara Bucciarelli-Ducci In X
Abstract: This consensus paper provides a framework for grading of severity of cardiovascular magnetic resonance (CMR) imaging-based assessment of chamber size, function, and aortic measurements. This does not currently exist for CMR measures. Differences exist in the normal reference values between echocardiography and CMR along with differences in methods used to derive these. We feel that this document will significantly complement the current literature and provide a practical guide for clinicians in daily reporting and interpretation of CMR scans. This manuscript aims to complement a recent comprehensive review of CMR normal value publications to recommend cut-off values required for severity grading. Standardization of severity grading for clinically useful CMR parameters is encouraged to lead to clearer and easier communication with referring clinicians and may contribute to better patient care. To this end, the European Association of Cardiovascular Imaging (EACVI) has formed this expert panel that has critically reviewed the literature and has come to a consensus on approaches to severity grading for commonly quantified CMR parameters.
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Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy.

Open Access Issue 12 Vol 20 Published on 2019-12-01 PMID 31504370 PMCID PMC6868494
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Keywords: Echocardiography, hypertrophic cardiomyopathy, Diastolic Dysfunction, Cardiovascular Magnetic Resonance, Pulmonary Blood Volume
DOI: https://doi.org/10.1093/ehjci/jez213
Authors: Fabrizio Ricci In X Nay Aung In X Ross Thomson In X Redha Boubertakh In X Claudia Camaioni In X Sara Doimo In X Mihir M Sanghvi In X Kenneth Fung In X Mohammed Y Khanji In X Aaron Lee In X James Malcolmson In X Cesare Mantini In X José Paiva In X Sabina Gallina In X Artur Fedorowski In X Saidi A Mohiddin In X Giovanni Donato Aquaro In X Steffen E Petersen In X
Abstract:

Aims

The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM.

Methods and results

We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03).

Conclusion

PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.
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CHA2DS2VASc score and adverse outcomes in middle-aged individuals without atrial fibrillation.

Issue 18 Vol 26 Published on 2019-12-01 PMID 31409109 PMCID N/A
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Keywords: Anticoagulation, Atrial fibrillation, Ischaemic Stroke, Cardiovascular Risk, Thromboembolic Risk
DOI: https://doi.org/10.1177/2047487319868320
Authors: Giulia Renda In X Fabrizio Ricci In X Giuseppe Patti In X Nay Aung In X Steffen E Petersen In X Sabina Gallina In X Viktor Hamrefors In X Olle Melander In X Richard Sutton In X Gunnar Engstrom In X Raffaele De Caterina In X Artur Fedorowski In X
Abstract:

Aims

The CHA2DS2VASc score is used to evaluate the risk of thromboembolic events in patients with non-valvular atrial fibrillation. We assessed the prognostic yield of CHA2DS2VASc for new-onset atrial fibrillation, cardiovascular morbidity and mortality in a non-atrial fibrillation population.

Methods

We analysed a population-based cohort of 22,179 middle-aged individuals with (n = 3542) and without (n = 18,367) a history of atrial fibrillation; we grouped the population into five CHA2DS2VASc strata (0-1-2-3-≥4), and compared the risk of major adverse cerebro-cardiovascular events and mortality. Furthermore, we analysed the annual incidence of atrial fibrillation across different CHA2DS2VASc strata.

Results

Over a median follow-up of 15 years, 1572 patients (6.9%) had ischaemic strokes, 2162 (9.5%) coronary events and 5899 (26%) died. The cumulative incidence of ischaemic stroke in CHA2DS2VASc ≥ 4 subjects without atrial fibrillation was similar to patients with atrial fibrillation and CHA2DS2VASc 2, with a 10-year crude incidence rate of 0.91 (95% confidence interval (CI) 0.68-1.19) and 1.13 (95% CI 0.93-1.36) ischaemic strokes per 100 patient-years, respectively. CHA2DS2VASc in a non-atrial fibrillation population showed higher predictive accuracy for ischaemic stroke compared with an atrial fibrillation population (area under the curve 0.60 vs. 0.56; P = 0.001). In multivariable Cox regression analysis, CHA2DS2VASc ≥ 2 was an independent predictor of all-cause death (adjusted hazard ratio (aHR) 2.58; 95% CI 2.42-2.76), cardiovascular death (aHR 3.40; 95% CI 2.98-3.89), ischaemic stroke (aHR 2.20; 95% CI 1.92-2.53) and coronary events (aHR 1.83; 95% CI 1.63-2.04). The cumulative incidence of atrial fibrillation was greater with increasing CHA2DS2VASc strata, with an absolute annual incidence of more than 2% per year if CHA2DS2VASc ≥ 4.

Conclusion

The CHA2DS2VASc score is a sensitive tool for predicting new-onset atrial fibrillation and adverse outcomes in subjects both with and without atrial fibrillation.
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Children Use Regions in the Visual Processing and Executive Function Networks during a Subsequent Memory Reading Task.

Issue 12 Vol 29 Published on 2019-12-01 PMID 30927366 PMCID PMC7049310
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Keywords: Memory, Children, Functional MRI, Cognitive Control, Visual Processing
DOI: https://doi.org/10.1093/cercor/bhz057
Authors: Rola Farah In X Rebecca S Coalson In X Steven E Petersen In X Bradley L Schlaggar In X Tzipi Horowitz-Kraus In X
Abstract: Memory encoding is a critical process for memory function, which is foundational for cognitive functioning including reading, and has been extensively studied using subsequent memory tasks. Research in adults using such tasks indicates the participation of visual and cognitive-control systems in remembered versus forgotten words. However, given the known developmental trajectories of these systems, the functional neuroanatomy of memory encoding in children may be different than in adults. We examined brain activation for silent word reading and checkerboard viewing during an event-related reading task in 8-12 year-old children. Results indicate greater activation for checkerboard viewing than lexical processing in early visual regions, as well as for lexical processing versus checkerboard viewing in regions in left sensorimotor mouth, cingulo-opercular and dorsal-attention networks. Greater activation for remembered than forgotten words was observed in bilateral visual system and left lateralized regions within the ventral- and dorsal-attention, cingulo-opercular and fronto-parietal networks. These findings suggest a relatively mature reliance on the cognitive-control system, but greater reliance on the visual system in children when viewing words subsequently remembered. The location of regions with greater activity for remembered words reinforces the involvement of the attention and cognitive-control systems in subsequent memory in reading.
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Trait-like variants in human functional brain networks.

Issue 45 Vol 116 Published on 2019-11-01 PMID 31611415 PMCID PMC6842602
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Keywords: Networks, Individual Differences, Functional Connectivity, Resting-state
DOI: https://doi.org/10.1073/pnas.1902932116
Authors: Benjamin A Seitzman In X Caterina Gratton In X Timothy O Laumann In X Evan M Gordon In X Babatunde Adeyemo In X Ally Dworetsky In X Brian T Kraus In X Adrian W Gilmore In X Jeffrey J Berg In X Mario Ortega In X Annie Nguyen In X Deanna J Greene In X Kathleen B McDermott In X Steven M Nelson In X Christina N Lessov-Schlaggar In X Bradley L Schlaggar In X Nico U F Dosenbach In X Steven E Petersen In X
Abstract: Resting-state functional magnetic resonance imaging (fMRI) has provided converging descriptions of group-level functional brain organization. Recent work has revealed that functional networks identified in individuals contain local features that differ from the group-level description. We define these features as network variants. Building on these studies, we ask whether distributions of network variants reflect stable, trait-like differences in brain organization. Across several datasets of highly-sampled individuals we show that 1) variants are highly stable within individuals, 2) variants are found in characteristic locations and associate with characteristic functional networks across large groups, 3) task-evoked signals in variants demonstrate a link to functional variation, and 4) individuals cluster into subgroups on the basis of variant characteristics that are related to differences in behavior. These results suggest that distributions of network variants may reflect stable, trait-like, functionally relevant individual differences in functional brain organization.
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Cohort Profile: DOC*X: a nationwide Danish occupational cohort with eXposure data - an open research resource.

Issue 5 Vol 48 Published on 2019-10-01 PMID 31730707 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ije/dyz110
Authors: Esben Meulengracht Flachs In X Sesilje Elise Bondo Petersen In X Henrik Albert Kolstad In X Vivi Schlünssen In X Susanne Wulff Svendsen In X Johnni Hansen In X Esben Budtz-Jørgensen In X Johan Hviid Andersen In X Ida Elisabeth Huitfeldt Madsen In X Jens Peter Ellekilde Bonde In X
Abstract: No Abstract Available
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Genome-Wide Analysis of Left Ventricular Image-Derived Phenotypes Identifies Fourteen Loci Associated With Cardiac Morphogenesis and Heart Failure Development.

Open Access Issue 16 Vol 140 Published on 2019-10-01 PMID 31554410 PMCID PMC6791514
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Keywords: Heart Failure, Genome-wide Association Study, Left ventricle
DOI: https://doi.org/10.1161/circulationaha.119.041161
Authors: Nay Aung In X Jose D Vargas In X Chaojie Yang In X Claudia P Cabrera In X Helen R Warren In X Kenneth Fung In X Evan Tzanis In X Michael R Barnes In X Jerome I Rotter In X Kent D Taylor In X Ani W Manichaikul In X Joao A C Lima In X David A Bluemke In X Stefan K Piechnik In X Stefan Neubauer In X Patricia B Munroe In X Steffen E Petersen In X
Abstract:

Background

The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear at present.

Methods

The LV parameters were measured from the cardiovascular magnetic resonance studies of the UK Biobank. Genotyping was done using Affymetrix arrays, augmented by imputation. We performed genome-wide association studies of 6 LV traits-LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction, LV mass, and LV mass to end-diastolic volume ratio. The replication analysis was performed in the MESA study (Multi-Ethnic Study of Atherosclerosis). We identified the candidate genes at genome-wide significant loci based on the evidence from extensive bioinformatic analyses. Polygenic risk scores were constructed from the summary statistics of LV genome-wide association studies to predict the heart failure events.

Results

The study comprised 16 923 European UK Biobank participants (mean age 62.5 years; 45.8% men) without prevalent myocardial infarction or heart failure. We discovered 14 genome-wide significant loci (3 loci each for LV end-diastolic volume, LV end-systolic volume, and LV mass to end-diastolic volume ratio; 4 loci for LV ejection fraction, and 1 locus for LV mass) at a stringent P<1×10-8. Three loci were replicated at Bonferroni significance and 7 loci at nominal significance (P<0.05 with concordant direction of effect) in the MESA study (n=4383). Follow-up bioinformatic analyses identified 28 candidate genes that were enriched in the cardiac developmental pathways and regulation of the LV contractile mechanism. Eight genes (TTN, BAG3, GRK5, HSPB7, MTSS1, ALPK3, NMB, and MMP11) supported by at least 2 independent lines of in silico evidence were implicated in the cardiac morphogenesis and heart failure development. The polygenic risk scores of LV phenotypes were predictive of heart failure in a holdout UK Biobank sample of 3106 cases and 224 134 controls (odds ratio 1.41, 95% CI 1.26 - 1.58, for the top quintile versus the bottom quintile of the LV end-systolic volume risk score).

Conclusions

We report 14 genetic loci and indicate several candidate genes that not only enhance our understanding of the genetic architecture of prognostically important LV phenotypes but also shed light on potential novel therapeutic targets for LV remodeling.
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A Multicenter, Scan-Rescan, Human and Machine Learning CMR Study to Test Generalizability and Precision in Imaging Biomarker Analysis.

Issue 10 Vol 12 Published on 2019-10-01 PMID 31547689 PMCID N/A
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Keywords: Artificial intelligence, Image processing, Ventricular function, Left ventricular remodeling, Magnetic Resonance Imaging, Cine
DOI: https://doi.org/10.1161/circimaging.119.009214
Authors: Anish Bhuva In X Wenjia Bai In X Clement Lau In X Rhodri Davies In X Yang Ye In X Heeraj Bulluck In X Elisa McAlindon In X Veronica Culotta In X Peter Swoboda In X Gabriella Captur In X Thomas Treibel In X Joao Augusto In X Kristopher Knott In X Andreas Seraphim In X Graham Cole In X Steffen Petersen In X Nicola Edwards In X John Greenwood In X Chiara Bucciarelli-Ducci In X Alun Hughes In X Daniel Rueckert In X James Moon In X Charlotte Manisty In X
Abstract:

Background

Automated analysis of cardiac structure and function using machine learning (ML) has great potential, but is currently hindered by poor generalizability. Comparison is traditionally against clinicians as a reference, ignoring inherent human inter- and intraobserver error, and ensuring that ML cannot demonstrate superiority. Measuring precision (scan:rescan reproducibility) addresses this. We compared precision of ML and humans using a multicenter, multi-disease, scan:rescan cardiovascular magnetic resonance data set.

Methods

One hundred ten patients (5 disease categories, 5 institutions, 2 scanner manufacturers, and 2 field strengths) underwent scan:rescan cardiovascular magnetic resonance (96% within one week). After identification of the most precise human technique, left ventricular chamber volumes, mass, and ejection fraction were measured by an expert, a trained junior clinician, and a fully automated convolutional neural network trained on 599 independent multicenter disease cases. Scan:rescan coefficient of variation and 1000 bootstrapped 95% CIs were calculated and compared using mixed linear effects models.

Results

Clinicians can be confident in detecting a 9% change in left ventricular ejection fraction, with greater than half of coefficient of variation attributable to intraobserver variation. Expert, trained junior, and automated scan:rescan precision were similar (for left ventricular ejection fraction, coefficient of variation 6.1 [5.2%-7.1%], P=0.2581; 8.3 [5.6%-10.3%], P=0.3653; 8.8 [6.1%-11.1%], P=0.8620). Automated analysis was 186× faster than humans (0.07 versus 13 minutes).

Conclusions

Automated ML analysis is faster with similar precision to the most precise human techniques, even when challenged with real-world scan:rescan data. Assessment of multicenter, multi-vendor, multi-field strength scan:rescan data (available at www.thevolumesresource.com) permits a generalizable assessment of ML precision and may facilitate direct translation of ML to clinical practice.
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High-fidelity mapping of repetition-related changes in the parietal memory network.

Issue N/A Vol 199 Published on 2019-10-01 PMID 31175969 PMCID PMC6688913
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Keywords: Memory, fMRI, Familiarity, Retrieval, Parietal cortex, Highly-sampled Human Subjects
DOI: https://doi.org/10.1016/j.neuroimage.2019.06.011
Authors: Adrian W Gilmore In X Steven M Nelson In X Timothy O Laumann In X Evan M Gordon In X Jeffrey J Berg In X Deanna J Greene In X Caterina Gratton In X Annie L Nguyen In X Mario Ortega In X Catherine R Hoyt In X Rebecca S Coalson In X Bradley L Schlaggar In X Steven E Petersen In X Nico U F Dosenbach In X Kathleen B McDermott In X
Abstract: fMRI studies of human memory have identified a "parietal memory network" (PMN) that displays distinct responses to novel and familiar stimuli, typically deactivating during initial encoding but robustly activating during retrieval. The small size of PMN regions, combined with their proximity to the neighboring default mode network, makes a targeted assessment of their responses in highly sampled subjects important for understanding information processing within the network. Here, we describe an experiment in which participants made semantic decisions about repeatedly-presented stimuli, assessing PMN BOLD responses as items transitioned from experimentally novel to repeated. Data are from the highly-sampled subjects in the Midnight Scan Club dataset, enabling a characterization of BOLD responses at both the group and single-subject level. Across all analyses, PMN regions deactivated in response to novel stimuli and displayed changes in BOLD activity across presentations, but did not significantly activate to repeated items. Results support only a portion of initially hypothesized effects, in particular suggesting that novelty-related deactivations may be less susceptible to attentional/task manipulations than are repetition-related activations within the network. This in turn suggests that novelty and familiarity may be processed as separable entities within the PMN.
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Changes in Cardiac Morphology and Function in Individuals With Diabetes Mellitus: The UK Biobank Cardiovascular Magnetic Resonance Substudy.

Open Access Issue 9 Vol 12 Published on 2019-09-01 PMID 31522551 PMCID PMC7099857
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Keywords: Diabetes mellitus, Magnetic Resonance Imaging, Heart Disease, Cardiomyopathies, cardiovascular
DOI: https://doi.org/10.1161/circimaging.119.009476
Authors: Magnus T Jensen In X Kenneth Fung In X Nay Aung In X Mihir M Sanghvi In X Sucharitha Chadalavada In X Jose M Paiva In X Mohammed Y Khanji In X Martina C de Knegt In X Elena Lukaschuk In X Aaron M Lee In X Ahmet Barutcu In X Edd Maclean In X Valentina Carapella In X Jackie Cooper In X Alistair Young In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging.

Methods

Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ≥50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status.

Results

A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: -0.86% [-1.8 to 0.5]; P=0.065), LV mass (-0.13 g/m2 [-1.6 to 1.3], P=0.86), or right ventricular ejection fraction (-0.23% [-1.2 to 0.8], P=0.65). However, both LV and right ventricular volumes were significantly smaller in DM, (LV end-diastolic volume/m2: -3.46 mL/m2 [-5.8 to -1.2], P=0.003, right ventricular end-diastolic volume/m2: -4.2 mL/m2 [-6.8 to -1.7], P=0.001, LV stroke volume/m2: -3.0 mL/m2 [-4.5 to -1.5], P<0.001; right ventricular stroke volume/m2: -3.8 mL/m2 [-6.5 to -1.1], P=0.005), LV mass/volume: 0.026 (0.01 to 0.04) g/mL, P=0.006. Both left atrial and right atrial emptying fraction were lower in DM (right atrial emptying fraction: -6.2% [-10.2 to -2.1], P=0.003; left atrial emptying fraction:-3.5% [-6.9 to -0.1], P=0.043). LV global circumferential strain was impaired in DM (coefficient [95% CI]: 0.38% [0.01 to 0.7], P=0.045).

Conclusions

In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally.
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2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC).

Issue 3 Vol 54 Published on 2019-09-01 PMID 31473594 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1183/13993003.01647-2019
Authors: Stavros V Konstantinides In X Guy Meyer In X Cecilia Becattini In X Héctor Bueno In X Geert-Jan Geersing In X Veli-Pekka Harjola In X Menno V Huisman In X Marc Humbert In X Catriona Sian Jennings In X David Jiménez In X Nils Kucher In X Irene Marthe Lang In X Mareike Lankeit In X Roberto Lorusso In X Lucia Mazzolai In X Nicolas Meneveau In X Fionnuala Ní Áinle In X Paolo Prandoni In X Piotr Pruszczyk In X Marc Righini In X Adam Torbicki In X Eric Van Belle In X José Luis Zamorano In X In X
Abstract: No Abstract Available
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Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): Study design for a controlled study of diagnostic accuracy.

Issue N/A Vol 215 Published on 2019-09-01 PMID 31323454 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.ahj.2019.03.016
Authors: Laust Dupont Rasmussen In X Simon Winther In X Jelmer Westra In X Christin Isaksen In X June Anita Ejlersen In X Lau Brix In X Jane Kirk In X Grazina Urbonaviciene In X Hanne Maare Søndergaard In X Osama Hammid In X Samuel Emil Schmidt In X Lars Lyhne Knudsen In X Lene Helleskov Madsen In X Lars Frost In X Steffen E Petersen In X Lars Christian Gormsen In X Evald Høj Christiansen In X Ashkan Eftekhari In X Niels Ramsing Holm In X Mette Nyegaard In X Amedeo Chiribiri In X Hans Erik Bøtker In X Morten Böttcher In X
Abstract:

Background

Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography (82Rb-PET), and CT-derived fractional flow reserve (FFRCT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard.

Methods

Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFRCT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion.

Discussion

The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.
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Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion.

Issue 9 Vol 35 Published on 2019-09-01 PMID 31016502 PMCID N/A
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DOI: https://doi.org/10.1007/s10554-019-01604-x
Authors: L Nissen In X S Winther In X J Westra In X J A Ejlersen In X C Isaksen In X A Rossi In X N R Holm In X G Urbonaviciene In X L C Gormsen In X L H Madsen In X E H Christiansen In X M Maeng In X L L Knudsen In X L Frost In X L Brix In X H E Bøtker In X S E Petersen In X M Bøttcher In X
Abstract: We aimed to identify factors influencing the sensitivity of perfusion imaging after an initial positive coronary computed tomography angiography (CCTA) using invasive coronary angiography (ICA) with conditional fractional flow reserve (FFR) as reference. Secondly we aimed to identify factors associated with revascularisation and to evaluate treatment outcome after ICA. We analysed 292 consecutive patients with suspected significant coronary artery disease (CAD) at CCTA, who underwent perfusion imaging with either cardiac magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS) followed by ICA with conditional FFR. Stratified analysis and uni- and multiple logistic regression analyses were performed to identify predictors of diagnostic agreement between perfusion scans and ICA and predictors of revascularisation. Myocardial ischemia evaluated with perfusion scans was present in 65/292 (22%) while 117/292 (40%) had obstructive CAD evaluated by ICA. Revascularisation rate was 90/292 (31%). The overall sensitivity for perfusion scans was 39% (30-48), specificity 89% (83-93), PPV 69% (57-80) and NPV 68% (62-74). Stratified analysis showed higher sensitivities in patients with multi-vessel disease at CCTA 49% (37-60) and typical chest pain 50% (37-60). Predictors of revascularisation were multi-vessel disease by CCTA (OR 3.51 [1.91-6.48]) and a positive perfusion scan (OR 4.69 [2.49-8.83]). The sensitivity for perfusion scans after CCTA was highest in patients with typical angina and multiple lesions at CCTA and predicted diagnostic agreement between perfusion scans and ICA. Abnormal perfusion and multi vessel disease at CCTA predicted revascularisation.
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The year 2018 in the European Heart Journal - Cardiovascular Imaging: Part I.

Issue 8 Vol 20 Published on 2019-08-01 PMID 31211353 PMCID N/A
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Keywords: Echocardiography, CT, PET, Nuclear Cardiology, Cmr
DOI: https://doi.org/10.1093/ehjci/jez133
Authors: Thor Edvardsen In X Kristina H Haugaa In X Steffen E Petersen In X Alessia Gimelli In X Erwan Donal In X Gerald Maurer In X Bogdan A Popescu In X Bernard Cosyns In X
Abstract: The European Heart Journal - Cardiovascular Imaging has become one of the leading multimodality cardiovascular imaging journal, since it was launched in 2012. The impact factor is an impressive 8.366 and it is now established as one of the top 10 cardiovascular journals. The journal is the most important cardiovascular imaging journal in Europe. The most important studies from 2018 will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
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Quantitative CMR population imaging on 20,000 subjects of the UK Biobank imaging study: LV/RV quantification pipeline and its evaluation.

Issue N/A Vol 56 Published on 2019-08-01 PMID 31154149 PMCID N/A
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Keywords: Quality assessment, Cardiac Mr, Uk Biobank, Statistical Shape Models, Population Imaging, Fully Automatic Analysis, Cardiac Functional Indexes, Cardiac Morphological Analysis
DOI: https://doi.org/10.1016/j.media.2019.05.006
Authors: Rahman Attar In X Marco Pereañez In X Ali Gooya In X Xènia Albà In X Le Zhang In X Milton Hoz de Vila In X Aaron M Lee In X Nay Aung In X Elena Lukaschuk In X Mihir M Sanghvi In X Kenneth Fung In X Jose Miguel Paiva In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk. Such studies pose new challenges requiring automatic image analysis. To date, few large-scale population-level cardiac imaging studies have been conducted. One such study stands out for its sheer size, careful implementation, and availability of top quality expert annotation; the UK Biobank (UKB). The resulting massive imaging datasets (targeting ca. 100,000 subjects) has put published approaches for cardiac image quantification to the test. In this paper, we present and evaluate a cardiac magnetic resonance (CMR) image analysis pipeline that properly scales up and can provide a fully automatic analysis of the UKB CMR study. Without manual user interactions, our pipeline performs end-to-end image analytics from multi-view cine CMR images all the way to anatomical and functional bi-ventricular quantification. All this, while maintaining relevant quality controls of the CMR input images, and resulting image segmentations. To the best of our knowledge, this is the first published attempt to fully automate the extraction of global and regional reference ranges of all key functional cardiovascular indexes, from both left and right cardiac ventricles, for a population of 20,000 subjects imaged at 50 time frames per subject, for a total of one million CMR volumes. In addition, our pipeline provides 3D anatomical bi-ventricular models of the heart. These models enable the extraction of detailed information of the morphodynamics of the two ventricles for subsequent association to genetic, omics, lifestyle habits, exposure information, and other information provided in population imaging studies. We validated our proposed CMR analytics pipeline against manual expert readings on a reference cohort of 4620 subjects with contour delineations and corresponding clinical indexes. Our results show broad significant agreement between the manually obtained reference indexes, and those automatically computed via our framework. 80.67% of subjects were processed with mean contour distance of less than 1 pixel, and 17.50% with mean contour distance between 1 and 2 pixels. Finally, we compare our pipeline with a recently published approach reporting on UKB data, and based on deep learning. Our comparison shows similar performance in terms of segmentation accuracy with respect to human experts.
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Right ventricular shape and function: cardiovascular magnetic resonance reference morphology and biventricular risk factor morphometrics in UK Biobank.

Open Access Issue 1 Vol 21 Published on 2019-07-01 PMID 31315625 PMCID PMC6637624
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Keywords: Ventricular function, Atlases, Cardiovascular Magnetic Resonance, Uk Biobank
DOI: https://doi.org/10.1186/s12968-019-0551-6
Authors: Charlène Mauger In X Kathleen Gilbert In X Aaron M Lee In X Mihir M Sanghvi In X Nay Aung In X Kenneth Fung In X Valentina Carapella In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Avan Suinesiaputra In X Alistair A Young In X
Abstract:

Background

The associations between cardiovascular disease (CVD) risk factors and the biventricular geometry of the right ventricle (RV) and left ventricle (LV) have been difficult to assess, due to subtle and complex shape changes. We sought to quantify reference RV morphology as well as biventricular variations associated with common cardiovascular risk factors.

Methods

A biventricular shape atlas was automatically constructed using contours and landmarks from 4329 UK Biobank cardiovascular magnetic resonance (CMR) studies. A subdivision surface geometric mesh was customized to the contours using a diffeomorphic registration algorithm, with automatic correction of slice shifts due to differences in breath-hold position. A reference sub-cohort was identified consisting of 630 participants with no CVD risk factors. Morphometric scores were computed using linear regression to quantify shape variations associated with four risk factors (high cholesterol, high blood pressure, obesity and smoking) and three disease factors (diabetes, previous myocardial infarction and angina).

Results

The atlas construction led to an accurate representation of 3D shapes at end-diastole and end-systole, with acceptable fitting errors between surfaces and contours (average error less than 1.5 mm). Atlas shape features had stronger associations than traditional mass and volume measures for all factors (p < 0.005 for each). High blood pressure was associated with outward displacement of the LV free walls, but inward displacement of the RV free wall and thickening of the septum. Smoking was associated with a rounder RV with inward displacement of the RV free wall and increased relative wall thickness.

Conclusion

Morphometric relationships between biventricular shape and cardiovascular risk factors in a large cohort show complex interactions between RV and LV morphology. These can be quantified by z-scores, which can be used to study the morphological correlates of disease.
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Personalized E-Coaching in Cardiovascular Risk Reduction: A Randomized Controlled Trial.

Open Access Issue 1 Vol 85 Published on 2019-07-01 PMID 31298823 PMCID PMC6634325
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DOI: https://doi.org/10.5334/aogh.2496
Authors: Mohammed Y Khanji In X Armida Balawon In X Redha Boubertakh In X Leonard Hofstra In X Jagat Narula In X Myriam Hunink In X Francesca Pugliese In X Steffen E Petersen In X
Abstract:

Objectives

To assess whether electronic (e-) coaching, using personalized web-based lifestyle and risk factor counselling with additional email prompts, provides additional risk reduction when added to standard of care (SOC) in individuals at increased risk.

Methods

Between June 2013 and May 2015, 402 participants were allocated 1:1 to e-coaching and SOC versus SOC. Participants free of manifest cardiovascular disease, with internet access, and a 10-year QRISK2 cardiovascular risk of ≥10% were enrolled. Change in oscillometric carotid-femoral pulse wave velocity (PWV) from baseline to six months was the primary endpoint. Secondary outcomes included change in blood pressure (BP), weight, and risk scores. Analysis was by intention to treat.

Results

Mean (±SD) age was 65.5 (5.6) years with 37% females. Primary outcome data were available for 94%. There was no difference in PWV reductions between e-coaching and standard of care groups (-0.16 m/s vs. -0.25 m/s, 95% confidence interval -0.39 to 0.22, p = 0.56). There were no differences in the improvement between groups for BP, weight, Framingham, or QRISK2 scores. Pulse wave velocity change was more favorable in those with a higher level of education (p = 0.04), but was not associated with age, gender, presence of diabetes, baseline QRISK2 score, or logins to the website.

Conclusions

In individuals at increased cardiovascular risk, a comprehensive 'health check' program modestly reduced future risk. Personalized e-coaching did not provide added risk reduction. Currently there is no evidence to routinely recommend e-coaching in cardiovascular health check programs.

Trial registration

HAPPY London ClinicalTrials.gov: NCT01911910.
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Physical activity and left ventricular trabeculation in the UK Biobank community-based cohort study.

Open Access Issue 13 Vol 105 Published on 2019-07-01 PMID 30723101 PMCID PMC6582810
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Keywords: Cardiac Magnetic Resonance (Cmr) Imaging
DOI: https://doi.org/10.1136/heartjnl-2018-314155
Authors: Simon P Woodbridge In X Nay Aung In X Jose M Paiva In X Mihir M Sanghvi In X Filip Zemrak In X Kenneth Fung In X Steffen E Petersen In X
Abstract:

Objective

Vigorous physical activity (PA) in highly trained athletes has been associated with heightened left ventricular (LV) trabeculation extent. It has therefore been hypothesised that LV trabeculation extent may participate in exercise-induced physiological cardiac remodelling. Our cross-sectional observational study aimed to ascertain whether there is a 'dose-response' relationship between PA and LV trabeculation extent and whether this could be identified at opposite PA extremes.

Methods

In a cohort of 1030 individuals from the community-based UK Biobank study (male/female ratio: 0.84, mean age: 61 years), PA was measured via total metabolic equivalent of task (MET) min/week and 7-day average acceleration, and trabeculation extent via maximal non-compaction/compaction ratio (NC/C) in long-axis images of cardiovascular magnetic resonance studies. The relationship between PA and NC/C was assessed by multivariate regression (adjusting for potential confounders) as well as between demographic, anthropometric and LV phenotypic parameters and NC/C.

Results

There was no significant linear relationship between PA and NC/C (full adjustment, total MET-min/week: ß=-0.0008, 95% CI -0.039 to -0.037, p=0.97; 7-day average acceleration: ß=-0.047, 95% CI -0.110 to -0.115, p=0.13, per IQR increment in PA), or between extreme PA quintiles (full adjustment, total MET-min/week: ß=-0.026, 95% CI -0.146 to -0.094, p=0.67; 7-day average acceleration: ß=-0.129, 95% CI -0.299 to -0.040, p=0.49), across all adjustment levels. A negative relationship was identified between left ventricular ejection fraction and NC/C, significantly modified by PA (ß difference=-0.006, p=0.03).

Conclusions

In a community-based general population cohort, there was no relationship at, or between, extremes, between PA and NC/C, suggesting that at typical general population PA levels, trabeculation extent is not influenced by PA changes.
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Two-Minute k-Space and Time-accelerated Aortic Four-dimensional Flow MRI: Dual-Center Study of Feasibility and Impact on Velocity and Wall Shear Stress Quantification.

Issue 2 Vol 1 Published on 2019-06-01 PMID 32076666 PMCID PMC6614912
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Keywords:
DOI: https://doi.org/10.1148/ryct.2019180008
Authors: Emilie Bollache In X Kristopher D Knott In X Kelly Jarvis In X Redha Boubertakh In X Ryan Scott Dolan In X Claudia Camaioni In X Louise Collins In X Paul Scully In X Sydney Rabin In X Thomas Treibel In X James C Carr In X Pim van Ooij In X Jeremy D Collins In X Julia Geiger In X James C Moon In X Alex J Barker In X Steffen E Petersen In X Michael Markl In X
Abstract:

Purpose

To investigate the two-center feasibility of highly k-space and time (k-t)-accelerated 2-minute aortic four-dimensional (4D) flow MRI and to evaluate its performance for the quantification of velocities and wall shear stress (WSS).

Materials and methods

This cross-sectional study prospectively included 68 participants (center 1, 11 healthy volunteers [mean age ± standard deviation, 61 years ± 15] and 16 patients with aortic disease [mean age, 60 years ± 10]; center 2, 14 healthy volunteers [mean age, 38 years ± 13] and 27 patients with aortic or cardiac disease [mean age, 78 years ± 18]). Each participant underwent highly accelerated 4D flow MRI (k-t acceleration, acceleration factor of 5) of the thoracic aorta. For comparison, conventional 4D flow MRI (acceleration factor of 2) was acquired in the participants at center 1 (n = 27). Regional aortic peak systolic velocities and three-dimensional WSS were quantified.

Results

k-t-accelerated scan times (center 1, 2:03 minutes ± 0:29; center 2, 2:06 minutes ± 0:20) were significantly reduced compared with conventional 4D flow MRI (center 1, 12:38 minutes ± 2:25; P < .0001). Overall good agreement was found between the two techniques (absolute differences ≤15%), but proximal aortic WSS was significantly underestimated in patients by using k-t-accelerated 4D flow when compared with conventional 4D flow (P ≤ .03). k-t-accelerated 4D flow MRI was reproducible (intra- and interobserver intraclass correlation coefficient ≥0.98) and identified significantly increased peak velocities and WSS in patients with stenotic (P ≤ .003) or bicuspid (P ≤ .04) aortic valves compared with healthy volunteers. In addition, k-t-accelerated 4D flow MRI-derived velocities and WSS were inversely related to age (r ≥-0.53; P ≤ .03) over all healthy volunteers.

Conclusion

k-t-accelerated aortic 4D flow MRI providing 2-minute scan times was feasible and reproducible at two centers. Although consistent healthy aging- and disease-related changes in aortic hemodynamics were observed, care should be taken when considering WSS, which can be underestimated in patients.© RSNA, 2019See also the commentary by François in this issue.
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Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants.

Open Access Issue 1 Vol 9 Published on 2019-06-01 PMID 31235810 PMCID PMC6591384
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Keywords:
DOI: https://doi.org/10.1038/s41598-019-45703-0
Authors: Kenneth Fung In X Julia Ramírez In X Helen R Warren In X Nay Aung In X Aaron M Lee In X Evan Tzanis In X Steffen E Petersen In X Patricia B Munroe In X
Abstract: Arterial stiffness index (ASI) is a non-invasive measure of arterial stiffness using infra-red finger sensors (photoplethysmography). It is a well-suited measure for large populations as it is relatively inexpensive to perform, and data can be acquired within seconds. These features raise interest in using ASI as a tool to estimate cardiovascular disease risk as prior work demonstrates increased arterial stiffness is associated with elevated systolic blood pressure, and ASI is predictive of cardiovascular disease and mortality. We conducted genome-wide association studies (GWASs) for ASI in 127,121 UK Biobank participants of European-ancestry. Our primary analyses identified variants at four loci reaching genome-wide significance (P < 5 × 10-8): TEX41 (rs1006923; P = 5.3 × 10-12), FOXO1 (rs7331212; P = 2.2 × 10-11), C1orf21 (rs1930290, P = 1.1 × 10-8) and MRVI1 (rs10840457, P = 3.4 × 10-8). Gene-based testing revealed three significant genes, the most significant gene was COL4A2 (P = 1.41 × 10-8) encoding type IV collagen. Other candidate genes at associated loci were also involved in smooth muscle tone regulation. Our findings provide new information for understanding the development of arterial stiffness.
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Emergent Functional Network Effects in Parkinson Disease.

Issue 6 Vol 29 Published on 2019-06-01 PMID 29878081 PMCID PMC6519699
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Keywords: fMRI, Parkinson disease, Networks, Functional Connectivity
DOI: https://doi.org/10.1093/cercor/bhy121
Authors: Caterina Gratton In X Jonathan M Koller In X William Shannon In X Deanna J Greene In X Baijayanta Maiti In X Abraham Z Snyder In X Steven E Petersen In X Joel S Perlmutter In X Meghan C Campbell In X
Abstract: The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks. We measured FC in a large, single-site study of nondemented PD (N = 107; OFF medications) and healthy controls (N = 46) incorporating rigorous quality control measures and comprehensive sampling of cortical, subcortical and cerebellar regions. We employed novel statistical approaches to determine group differences across the entire connectome, at the network-level, and for select brain regions. Group differences respected well-characterized network delineations producing a striking "block-wise" pattern of network-to-network effects. Surprisingly, these results demonstrate that the greatest FC differences involve sensorimotor, thalamic, and cerebellar networks, with notably smaller striatal effects. Split-half replication demonstrates the robustness of these results. Finally, block-wise FC correlations with behavior suggest that FC disruptions may contribute to clinical manifestations in PD. Overall, these results indicate a concerted breakdown of functional network interactions, remote from primary pathophysiology, and suggest that FC deficits in PD are related to emergent network-level phenomena rather than focal pathology.
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Evaluating the Prediction of Brain Maturity From Functional Connectivity After Motion Artifact Denoising.

Issue 6 Vol 29 Published on 2019-06-01 PMID 29850877 PMCID PMC6519700
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Keywords: Development, fMRI, Machine Learning, Functional Connectivity
DOI: https://doi.org/10.1093/cercor/bhy117
Authors: Ashley N Nielsen In X Deanna J Greene In X Caterina Gratton In X Nico U F Dosenbach In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The ability to make individual-level predictions from neuroanatomy has the potential to be particularly useful in child development. Previously, resting-state functional connectivity (RSFC) MRI has been used to successfully predict maturity and diagnosis of typically and atypically developing individuals. Unfortunately, submillimeter head motion in the scanner produces systematic, distance-dependent differences in RSFC and may contaminate, and potentially facilitate, these predictions. Here, we evaluated individual age prediction with RSFC after stringent motion denoising. Using multivariate machine learning, we found that 57% of the variance in individual RSFC after motion artifact denoising was explained by age, while 4% was explained by residual effects of head motion. When RSFC data were not adequately denoised, 50% of the variance was explained by motion. Reducing motion-related artifact also revealed that prediction did not depend upon characteristics of functional connections previously hypothesized to mediate development (e.g., connection distance). Instead, successful age prediction relied upon sampling functional connections across multiple functional systems with strong, reliable RSFC within an individual. Our results demonstrate that RSFC across the brain is sufficiently robust to make individual-level predictions of maturity in typical development, and hence, may have clinical utility for the diagnosis and prognosis of individuals with atypical developmental trajectories.
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Response by Aung and Petersen to Letter Regarding Article, "Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes: Insights From the UK Biobank Population Imaging Study".

Issue 15 Vol 139 Published on 2019-04-01 PMID 30958714 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1161/circulationaha.119.039916
Authors: Nay Aung In X Steffen E Petersen In X
Abstract: No Abstract Available
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Emergent Functional Network Effects in Parkinson Disease.

Issue 4 Vol 29 Published on 2019-04-01 PMID 30418543 PMCID PMC7302739
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Keywords:
DOI: https://doi.org/10.1093/cercor/bhy229
Authors: Caterina Gratton In X Jonathan M Koller In X William Shannon In X Deanna J Greene In X Baijayanta Maiti In X Abraham Z Snyder In X Steven E Petersen In X Joel S Perlmutter In X Meghan C Campbell In X
Abstract: No Abstract Available
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Automated quality control in image segmentation: application to the UK Biobank cardiovascular magnetic resonance imaging study.

Open Access Issue 1 Vol 21 Published on 2019-03-01 PMID 30866968 PMCID PMC6416857
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Keywords: Segmentation, Population Imaging, Automatic Quality Control
DOI: https://doi.org/10.1186/s12968-019-0523-x
Authors: Robert Robinson In X Vanya V Valindria In X Wenjia Bai In X Ozan Oktay In X Bernhard Kainz In X Hideaki Suzuki In X Mihir M Sanghvi In X Nay Aung In X José Miguel Paiva In X Filip Zemrak In X Kenneth Fung In X Elena Lukaschuk In X Aaron M Lee In X Valentina Carapella In X Young Jin Kim In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Chris Page In X Paul M Matthews In X Daniel Rueckert In X Ben Glocker In X
Abstract:

Background

The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale. However, it is important to be able to automatically detect when a segmentation method fails in order to avoid inclusion of wrong measurements into subsequent analyses which could otherwise lead to incorrect conclusions.

Methods

To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4800 cardiovascular magnetic resonance (CMR) scans. We then apply our method to a large cohort of 7250 CMR on which we have performed manual QC.

Results

We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using the predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4800 scans for which manual segmentations were available. We mimic real-world application of the method on 7250 CMR where we show good agreement between predicted quality metrics and manual visual QC scores.

Conclusions

We show that Reverse classification accuracy has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study.
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Impact of Measurement Variations in Right Atrial Structure and Function on Outcomes.

Issue 3 Vol 12 Published on 2019-03-01 PMID 30846129 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.jcmg.2018.12.028
Authors: Mohammed Y Khanji In X Kenneth Fung In X Erwan Donal In X Steffen E Petersen In X
Abstract: No Abstract Available
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Authors' Reply to Kindermann et al.'s Comment on: "Athlete's Heart: Diagnostic Challenges and Future Perspectives".

Issue 3 Vol 49 Published on 2019-03-01 PMID 30623298 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1007/s40279-018-01044-y
Authors: Carlo De Innocentiis In X Fabrizio Ricci In X Fabrizio Ricci In X Mohammed Y Khanji In X Nay Aung In X Claudio Tana In X Elvira Verrengia In X Steffen E Petersen In X Sabina Gallina In X
Abstract: No Abstract Available
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Independent Left Ventricular Morphometric Atlases Show Consistent Relationships with Cardiovascular Risk Factors: A UK Biobank Study.

Open Access Issue 1 Vol 9 Published on 2019-02-01 PMID 30718635 PMCID PMC6362245
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Keywords:
DOI: https://doi.org/10.1038/s41598-018-37916-6
Authors: Kathleen Gilbert In X Wenjia Bai In X Charlene Mauger In X Pau Medrano-Gracia In X Avan Suinesiaputra In X Aaron M Lee In X Mihir M Sanghvi In X Nay Aung In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Daniel Rueckert In X Alistair A Young In X
Abstract: Left ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort. We compared two independent LV atlases using MRI scans of 4547 UK Biobank participants: (i) a volume atlas derived by automatic non-rigid registration of image volumes to a common template, and (ii) a surface atlas derived from manually drawn epicardial and endocardial surface contours. The strength of associations between atlas principal components and cardiovascular risk factors (smoking, diabetes, high blood pressure, high cholesterol and angina) were quantified with logistic regression models and five-fold cross validation, using area under the ROC curve (AUC) and Akaike Information Criterion (AIC) metrics. Both atlases exhibited similar principal components, showed similar relationships with risk factors, and had stronger associations (higher AUC and lower AIC) than a reference model based on LV mass and volume, for all risk factors (DeLong p < 0.05). Morphometric variations associated with each risk factor could be quantified and visualized and were similar between atlases. UK Biobank LV shape atlases are robust to construction method and show stronger relationships with cardiovascular risk factors than mass and volume.
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Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.

Open Access Issue 2 Vol 20 Published on 2019-02-01 PMID 30358845 PMCID PMC6343081
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jey135
Authors: Betty Raman In X Rina Ariga In X Marco Spartera In X Sanjay Sivalokanathan In X Kenneth Chan In X Sairia Dass In X Steffen E Petersen In X Matthew J Daniels In X Jane Francis In X Robert Smillie In X Adam J Lewandowski In X Eric O Ohuma In X Christopher Rodgers In X Christopher M Kramer In X Masliza Mahmod In X Hugh Watkins In X Stefan Neubauer In X
Abstract:

Aims

Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications.

Methods and results

Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (ConclusionMyocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.
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Reward-related regions form a preferentially coupled system at rest.

Issue 2 Vol 40 Published on 2019-02-01 PMID 30251766 PMCID PMC6865378
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Keywords: Network, System, Nucleus accumbens, Reward, Self-regulation, Resting-state Fmri, Orbitofrontal Cortex
DOI: https://doi.org/10.1002/hbm.24377
Authors: Jeremy F Huckins In X Babatunde Adeyemo In X Fran M Miezin In X Jonathan D Power In X Evan M Gordon In X Timothy O Laumann In X Todd F Heatherton In X Steven E Petersen In X William M Kelley In X
Abstract: Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo-opercular and default systems, OFC regions show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.
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Cardiovascular magnetic resonance imaging for amyloidosis: The state-of-the-art.

Issue 2 Vol 29 Published on 2019-02-01 PMID 29983337 PMCID N/A
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Keywords: Amyloidosis, Cardiac Magnetic Resonance Imaging, Late Gadolinium Enhancement, T1 Mapping, Extracellular Volume
DOI: https://doi.org/10.1016/j.tcm.2018.06.011
Authors: Chun Xiang Tang In X Steffen E Petersen In X Mihir M Sanghvi In X Guang Ming Lu In X Long Jiang Zhang In X
Abstract: Amyloidosis results from insoluble precursor proteins being deposited in the extracellular compartment. The prognosis of the disease is predominantly determined by cardiac involvement due to amyloid accumulation that contributes to cardiac dysfunction and disturbed conduction of cardiac electrical signals. The clinical and radiological manifestations of amyloidosis are often non-specific, making amyloidosis a diagnostic challenge both for clinicians and radiologists. Cardiovascular magnetic resonance imaging, including conventional sequences, late gadolinium enhancement, T1 mapping and determination of extracellular volume fraction is a multi-dimensional modality for the assessment and diagnosis of cardiac amyloidosis and, in addition, is an excellent tool for risk stratification and disease tracking.
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Does self-reported pregnancy loss identify women at risk of an adverse cardiovascular phenotype in later life? Insights from UK Biobank.

Open Access Issue 10 Vol 14 Published on 2019-01-01 PMID 31644534 PMCID PMC6808447
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0223125
Authors: Einas Elmahi In X Mihir M Sanghvi In X Alexander Jones In X Christina Y L Aye In X Adam J Lewandowski In X Nay Aung In X Jackie A Cooper In X José Miguel Paiva In X Elena Lukaschuk In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X Paul Leeson In X
Abstract:

Introduction

Cardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk.

Methods

Pregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40-69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors.

Results

Data were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1).

Conclusion

Women who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk.
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Artificial Intelligence Will Transform Cardiac Imaging-Opportunities and Challenges.

Open Access Issue N/A Vol 6 Published on 2019-01-01 PMID 31552275 PMCID PMC6746883
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Keywords: Artificial intelligence, Cardiac Imaging, Cardiac Magnetic Resonance (Cmr), Cardiac Ct Angiogram, Deep Learning, Cardiac Nuclear Imaging, Echocardiagraphy
DOI: https://doi.org/10.3389/fcvm.2019.00133
Authors: Steffen E Petersen In X Musa Abdulkareem In X Tim Leiner In X
Abstract: Artificial intelligence (AI) using machine learning techniques will change healthcare as we know it. While healthcare AI applications are currently trailing behind popular AI applications, such as personalized web-based advertising, the pace of research and deployment is picking up and about to become disruptive. Overcoming challenges such as patient and public support, transparency over the legal basis for healthcare data use, privacy preservation, technical challenges related to accessing large-scale data from healthcare systems not designed for Big Data analysis, and deployment of AI in routine clinical practice will be crucial. Cardiac imaging and imaging of other body parts is likely to be at the frontier for the development of applications as pattern recognition and machine learning are a significant strength of AI with practical links to image processing. Many opportunities in cardiac imaging exist where AI will impact patients, medical staff, hospitals, commissioners and thus, the entire healthcare system. This perspective article will outline our vision for AI in cardiac imaging with examples of potential applications, challenges and some lessons learnt in recent years.
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Using patient-reported outcome measures for primary percutaneous coronary intervention.

Open Access Issue 1 Vol 6 Published on 2019-01-01 PMID 30997123 PMCID PMC6443122
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Keywords: AMI, Feasibility, Retrospective, Health Status, Stemi, Health-related Quality Of Life, Response Rate, Patient Reported Outcome Measures, Emergency Admissions
DOI: https://doi.org/10.1136/openhrt-2018-000920
Authors: Esther Kwong In X Jenny Neuburger In X Steffen Erhard Petersen In X Nick Black In X
Abstract:

Introduction

Routine measurement of the outcome of myocardial infarction is usually limited to immediate morbidity and mortality. Our aim was to determine the response to patient-reported outcome measures (PROMs) 3 months later, identify response bias and explore the feasibility of comparing outcome with their recalled view of their prior health state.

Methods

Patients admitted with ST-segment-elevation myocardial infarction (STEMI) to five percutaneous coronary intervention centres were invited to complete a retrospective questionnaire containing the EQ-5D-3L and short form Seattle Angina Questionnaire (SAQ-7). Response rate for a 3-month mailed follow-up questionnaire and potential response biases were assessed. Patients' outcomes were compared with their baseline using χ2 and paired t-test to assess for differences.

Results

Of 392 patients contacted, 260 (66.3%) responded. Responders were more likely to be older, female, more affluent and have a higher EQ-5D at baseline. Three months after surgery, patients' SAQ-7 and angina symptom subscale returned to their baseline score. The physical limitation subscale score was worse than at baseline (79.9 vs 73.2, p=0.002), whereas the quality-of-life subscale was better (66.6 vs 73.9; p<0.001). The EQ-5D-3L index score was similar at 3 months to baseline (0.82 vs 0.79). Evidence of bias arising from responders being in better general health at baseline needs further investigation and, if confirmed, needs to be taken into account in interpreting PROMs data.

Conclusion

It is feasible to use PROMs routinely to assess the impact of emergency admissions of patients with STEMI. A larger demonstration project with more sites is needed to confirm these findings.
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Automated localization and quality control of the aorta in cine CMR can significantly accelerate processing of the UK Biobank population data.

Open Access Issue 2 Vol 14 Published on 2019-01-01 PMID 30763349 PMCID PMC6375606
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0212272
Authors: Luca Biasiolli In X Evan Hann In X Elena Lukaschuk In X Valentina Carapella In X Jose M Paiva In X Nay Aung In X Jennifer J Rayner In X Konrad Werys In X Kenneth Fung In X Henrike Puchta In X Mihir M Sanghvi In X Niall O Moon In X Ross J Thomson In X Katharine E Thomas In X Matthew D Robson In X Vicente Grau In X Steffen E Petersen In X Stefan Neubauer In X Stefan K Piechnik In X
Abstract:

Introduction

Aortic distensibility can be calculated using semi-automated methods to segment the aortic lumen on cine CMR (Cardiovascular Magnetic Resonance) images. However, these methods require visual quality control and manual localization of the region of interest (ROI) of ascending (AA) and proximal descending (PDA) aorta, which limit the analysis in large-scale population-based studies. Using 5100 scans from UK Biobank, this study sought to develop and validate a fully automated method to 1) detect and locate the ROIs of AA and PDA, and 2) provide a quality control mechanism.

Methods

The automated AA and PDA detection-localization algorithm followed these steps: 1) foreground segmentation; 2) detection of candidate ROIs by Circular Hough Transform (CHT); 3) spatial, histogram and shape feature extraction for candidate ROIs; 4) AA and PDA detection using Random Forest (RF); 5) quality control based on RF detection probability. To provide the ground truth, overall image quality (IQ = 0-3 from poor to good) and aortic locations were visually assessed by 13 observers. The automated algorithm was trained on 1200 scans and Dice Similarity Coefficient (DSC) was used to calculate the agreement between ground truth and automatically detected ROIs.

Results

The automated algorithm was tested on 3900 scans. Detection accuracy was 99.4% for AA and 99.8% for PDA. Aorta localization showed excellent agreement with the ground truth, with DSC ≥ 0.9 in 94.8% of AA (DSC = 0.97 ± 0.04) and 99.5% of PDA cases (DSC = 0.98 ± 0.03). AA×PDA detection probabilities could discriminate scans with IQ ≥ 1 from those severely corrupted by artefacts (AUC = 90.6%). If scans with detection probability < 0.75 were excluded (350 scans), the algorithm was able to correctly detect and localize AA and PDA in all the remaining 3550 scans (100% accuracy).

Conclusion

The proposed method for automated AA and PDA localization was extremely accurate and the automatically derived detection probabilities provided a robust mechanism to detect low quality scans for further human review. Applying the proposed localization and quality control techniques promises at least a ten-fold reduction in human involvement without sacrificing any accuracy.
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Mitral valve prolapse.

Issue 1 Vol 17 Published on 2019-01-01 PMID 30484338 PMCID N/A
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Keywords: Heart valves, Echocardiography, Mitral regurgitation, Cardiac surgery, Mitral Valve Prolapse, Degenerative Mitral Regurgitation
DOI: https://doi.org/10.1080/14779072.2019.1553619
Authors: Aeshah Althunayyan In X Steffen E Petersen In X Guy Lloyd In X Sanjeev Bhattacharyya In X
Abstract: Introduction: Mitral valve prolapse (MVP) is a common valve pathology with a spectrum of disease from isolated prolapse to myxomatous, multi-scallop Barlow's disease. The main complications relate to progression of mitral regurgitation, endocarditis, sudden death, and stroke. The timing of intervention in patients with asymptomatic severe mitral regurgitation is controversial. Areas covered: This article reviews the pathophysiology, genetics, clinical features, diagnostic imaging, complications, long-term outcomes, and indications for intervention in MVP. Expert commentary: Several key dilemmas in the management of MVP remain. Factors which influence progression of mitral regurgitation are unclear and therefore, we have no therapeutic targets to prevent progression. Evidence-based methods to reduce the risk of sudden death, stroke, and endocarditis have not been identified. In symptomatic patients with severe mitral regurgitation valve surgery is recommended. In asymptomatic patients, careful risk stratification incorporating markers of left ventricular dysfunction, atrial fibrillation, pulmonary hypertension, and valve reparability is required to identify the optimal timing of intervention.
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Restricted and Repetitive Behavior and Brain Functional Connectivity in Infants at Risk for Developing Autism Spectrum Disorder.

Issue 1 Vol 4 Published on 2019-01-01 PMID 30446435 PMCID PMC6557405
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Keywords: Infant, Functional magnetic resonance imaging, Brain Development, Autism Spectrum Disorder, Functional Connectivity, Restricted And Repetitive Behavior
DOI: https://doi.org/10.1016/j.bpsc.2018.09.008
Authors: Claire J McKinnon In X Adam T Eggebrecht In X Alexandre Todorov In X Jason J Wolff In X Jed T Elison In X Chloe M Adams In X Abraham Z Snyder In X Annette M Estes In X Lonnie Zwaigenbaum In X Kelly N Botteron In X Robert C McKinstry In X Natasha Marrus In X Alan Evans In X Heather C Hazlett In X Stephen R Dager In X Sarah J Paterson In X Juhi Pandey In X Robert T Schultz In X Martin A Styner In X Guido Gerig In X Bradley L Schlaggar In X Steven E Petersen In X Joseph Piven In X John R Pruett In X In X
Abstract:

Background

Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown.

Methods

Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory.

Results

Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior.

Conclusions

These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.
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Prevalence and Clinical Relevance of Extracardiac Findings in Cardiovascular Magnetic Resonance Imaging.

Issue 1 Vol 34 Published on 2019-01-01 PMID 30142138 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1097/rti.0000000000000360
Authors: Cesare Mantini In X Domenico Mastrodicasa In X Francesco Bianco In X Valentina Bucciarelli In X Michele Scarano In X Gianluca Mannetta In X Daniela Gabrielli In X Sabina Gallina In X Steffen E Petersen In X Fabrizio Ricci In X Filippo Cademartiri In X
Abstract:

Purpose

To assess the prevalence of extracardiac findings (ECF) during cardiovascular magnetic resonance (CMR) examinations and their downstream effect on clinical management.

Materials and methods

We retrospectively identified 500 consecutive patients. Trans-axial balanced steady-state free precession nongated images acquired from the upper thorax to the upper abdomen were evaluated independently by 2 radiologists. ECF were classified as nonsignificant (benign, with no need for further investigation), significant (mandatory to be reported/monitored), and major (clinically remarkable pathology, mandatory to be reported/investigated/treated). Fifteen-month clinical follow-up information was collected through hospital records.

Results

Of 500 patients, 108 (21.6%) showed a total of 153 ECF: 59 (11.8% of the entire study population; 38.5% of all ECF) nonsignificant, 76 (15.2%; 49.7%) significant, and 18 (3.6%; 11.8%) major ECF. The most frequent ECF were pleural effusion, hepatic cyst, renal cyst, and ascending aorta dilatation. Of 94 significant and major ECF, 46 were previously unknown and more common in older patients. Newly diagnosed major ECF (n=11, 2.2% of the entire study population, and 7.2% of all ECF)-including 5 tumors (1% of study population)-were confirmed by downstream evaluations and required specific treatment. Patients with major ECF were significantly older than patients without with major ECF. Newly diagnosed clinically significant and major ECF prompted downstream diagnostic tests in 44% and 100% of cases, respectively.

Conclusions

The detection of significant and major ECF is common during CMR reporting. The knowledge and the correct identification of most frequent ECF enable earlier diagnoses and faster treatment initiation of unknown extracardiac pathologies in patients referred to CMR imaging.
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Endomyocardial fibrosis masquerading as metastatic colorectal tumour; myocardial tissue characterization pivotal in guiding urgent surgical management.

Issue 45 Vol 39 Published on 2018-12-01 PMID 29912412 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/eurheartj/ehy242
Authors: Mohammed Y Khanji In X Muhamad Abd Razak In X Timothy J Bowker In X Steffen E Petersen In X
Abstract: No Abstract Available
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Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes: Insights From the UK Biobank Population Imaging Study.

Open Access Issue 20 Vol 138 Published on 2018-11-01 PMID 30524134 PMCID PMC6250297
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Keywords: Air pollution, Phenotypes, Magnetic Resonance Imaging
DOI: https://doi.org/10.1161/circulationaha.118.034856
Authors: Nay Aung In X Mihir M Sanghvi In X Filip Zemrak In X Aaron M Lee In X Jackie A Cooper In X Jose M Paiva In X Ross J Thomson In X Kenneth Fung In X Mohammed Y Khanji In X Elena Lukaschuk In X Valentina Carapella In X Young Jin Kim In X Patricia B Munroe In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders.

Methods

Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders.

Results

The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter <2.5 μm concentration was significantly associated with larger left ventricular end-diastolic volume and end-systolic volume (effect size = 0.82%, 95% CI, 0.09-1.55%, P=0.027; and effect size = 1.28%, 95% CI, 0.15-2.43%, P=0.027, respectively, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm) and right ventricular end-diastolic volume (effect size = 0.85%, 95% CI, 0.12-1.58%, P=0.023, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 μm). Likewise, higher nitrogen dioxide concentration was associated with larger biventricular volume. Distance from the major roads was the only metric associated with lower left ventricular mass (effect size = -0.74%, 95% CI, -1.3% to -0.18%, P=0.01, per interquartile range increment). Neither left and right atrial phenotypes nor left ventricular geometric remodeling patterns were influenced by the ambient pollutants.

Conclusions

In a large asymptomatic population with no prevalent cardiovascular disease, higher past exposure to particulate matter with an aerodynamic diameter <2.5 μm and nitrogen dioxide was associated with cardiac ventricular dilatation, a marker of adverse remodeling that often precedes heart failure development.
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Spatial and Temporal Organization of the Individual Human Cerebellum.

Issue 4 Vol 100 Published on 2018-11-01 PMID 30473014 PMCID PMC6351081
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Keywords: fMRI, Resting State Functional Connectivity, Individual Variability, Functional Networks, Frontoparietal Network, Temporal Lags, Human Cerebellum
DOI: https://doi.org/10.1016/j.neuron.2018.10.010
Authors: Scott Marek In X Joshua S Siegel In X Evan M Gordon In X Ryan V Raut In X Caterina Gratton In X Dillan J Newbold In X Mario Ortega In X Timothy O Laumann In X Babatunde Adeyemo In X Derek B Miller In X Annie Zheng In X Katherine C Lopez In X Jeffrey J Berg In X Rebecca S Coalson In X Annie L Nguyen In X Donna Dierker In X Andrew N Van In X Catherine R Hoyt In X Kathleen B McDermott In X Scott A Norris In X Joshua S Shimony In X Abraham Z Snyder In X Steven M Nelson In X Deanna M Barch In X Bradley L Schlaggar In X Marcus E Raichle In X Steven E Petersen In X Deanna J Greene In X Nico U F Dosenbach In X
Abstract: The cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related to specific functions in both structures. Recently, precision functional mapping of individuals revealed that functional networks in the cerebral cortex exhibit measurable individual specificity. Using the highly sampled Midnight Scan Club (MSC) dataset, we found the cerebellum contains reliable, individual-specific network organization that is significantly more variable than the cerebral cortex. The frontoparietal network, thought to support adaptive control, was the only network overrepresented in the cerebellum compared to the cerebral cortex (2.3-fold). Temporally, all cerebellar resting state signals lagged behind the cerebral cortex (125-380 ms), supporting the hypothesis that the cerebellum engages in a domain-general function in the adaptive control of all cortical processes.
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Athlete's Heart: Diagnostic Challenges and Future Perspectives.

Issue 11 Vol 48 Published on 2018-11-01 PMID 30251086 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1007/s40279-018-0985-2
Authors: Carlo De Innocentiis In X Fabrizio Ricci In X Fabrizio Ricci In X Mohammed Y Khanji In X Nay Aung In X Claudio Tana In X Elvira Verrengia In X Steffen E Petersen In X Sabina Gallina In X
Abstract: Distinguishing between adaptive and maladaptive cardiovascular response to exercise is crucial to prevent the unnecessary termination of an athlete's career and to minimize the risk of sudden death. This is a challenging task essentially due to the substantial phenotypic overlap between electrical and structural changes seen in the physiological athletic heart remodeling and pathological changes seen in inherited or acquired cardiomyopathies. Stress testing is an ideal tool to discriminate normal from abnormal cardiovascular response by unmasking subtle pathologic responses otherwise undetectable at rest. Treadmill or bicycle electrocardiography, transthoracic echocardiography, and cardiopulmonary exercise testing are common clinical investigations used in sports cardiology, specifically among participants presenting with resting electrocardiographic abnormalities, frequent premature ventricular beats, or non-sustained ventricular arrhythmias. In this setting, as well as in cases of left ventricular hypertrophy or asymptomatic left ventricular dysfunction, stress imaging and myocardial tissue characterization by cardiovascular magnetic resonance show promise. In this review, we aimed to reappraise current diagnostic schemes, screening strategies and novel approaches that may be used to distinguish adaptive remodeling patterns to physical exercise from early phenotypes of inherited or acquired pathological conditions commanding prompt intervention.
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The year 2017 in the European Heart Journal-Cardiovascular Imaging: Part I.

Issue 10 Vol 19 Published on 2018-10-01 PMID 30085023 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jey109
Authors: Bogdan A Popescu In X Steffen E Petersen In X Pál Maurovich-Horvat In X Kristina H Haugaa In X Erwan Donal In X Gerald Maurer In X Thor Edvardsen In X
Abstract: The European Heart Journal - Cardiovascular Imaging was launched in 2012. It has gained an impressive impact factor of 8.336 during its first 6 years and is now established as one of the top 10 cardiovascular journals in the world and the most important cardiovascular imaging journal in Europe. The most important studies published in the journal in 2017 will be highlighted in two reports. Part I will focus on studies about myocardial function, coronary artery disease and myocardial ischaemia, and emerging techniques and applications in cardiovascular imaging, whereas Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
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Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR imaging endpoints in clinical research: part I - analytical validation and clinical qualification.

Open Access Issue 1 Vol 20 Published on 2018-09-01 PMID 30231886 PMCID PMC6147157
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Keywords: Biomarker, Imaging, Cardiac Magnetic Resonance, Position Paper, Scmr
DOI: https://doi.org/10.1186/s12968-018-0484-5
Authors: Valentina O Puntmann In X Silvia Valbuena In X Rocio Hinojar In X Steffen E Petersen In X John P Greenwood In X Christopher M Kramer In X Raymond Y Kwong In X Gerry P McCann In X Colin Berry In X Eike Nagel In X In X
Abstract: Cardiovascular disease remains a leading cause of morbidity and mortality globally. Changing natural history of the disease due to improved care of acute conditions and ageing population necessitates new strategies to tackle conditions which have more chronic and indolent course. These include an increased deployment of safe screening methods, life-long surveillance, and monitoring of both disease activity and tailored-treatment, by way of increasingly personalized medical care. Cardiovascular magnetic resonance (CMR) is a non-invasive, ionising radiation-free method, which can support a significant number of clinically relevant measurements and offers new opportunities to advance the state of art of diagnosis, prognosis and treatment. The objective of the SCMR Clinical Trial Taskforce was to summarizes the evidence to emphasize where currently CMR-guided clinical care can indeed translate into meaningful use and efficient deployment of resources results in meaningful and efficient use. The objective of the present initiative was to provide an appraisal of evidence on analytical validation, including the accuracy and precision, and clinical qualification of parameters in disease context, clarifying the strengths and weaknesses of the state of art, as well as the gaps in the current evidence This paper is complementary to the existing position papers on standardized acquisition and post-processing ensuring robustness and transferability for widespread use. Themed imaging-endpoint guidance on trial design to support drug-discovery or change in clinical practice (part II), will be presented in a follow-up paper in due course. As CMR continues to undergo rapid development, regular updates of the present recommendations are foreseen.
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Automated cardiovascular magnetic resonance image analysis with fully convolutional networks.

Open Access Issue 1 Vol 20 Published on 2018-09-01 PMID 30217194 PMCID PMC6138894
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Keywords: Machine Learning, Fully Convolutional Networks, Cmr Image Analysis
DOI: https://doi.org/10.1186/s12968-018-0471-x
Authors: Wenjia Bai In X Matthew Sinclair In X Giacomo Tarroni In X Ozan Oktay In X Martin Rajchl In X Ghislain Vaillant In X Aaron M Lee In X Nay Aung In X Elena Lukaschuk In X Mihir M Sanghvi In X Filip Zemrak In X Kenneth Fung In X Jose Miguel Paiva In X Valentina Carapella In X Young Jin Kim In X Hideaki Suzuki In X Bernhard Kainz In X Paul M Matthews In X Steffen E Petersen In X Stefan K Piechnik In X Stefan Neubauer In X Ben Glocker In X Daniel Rueckert In X
Abstract:

Background

Cardiovascular resonance (CMR) imaging is a standard imaging modality for assessing cardiovascular diseases (CVDs), the leading cause of death globally. CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors. It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images.

Methods

Deep neural networks have shown a great potential in image pattern recognition and segmentation for a variety of tasks. Here we demonstrate an automated analysis method for CMR images, which is based on a fully convolutional network (FCN). The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4,875 subjects with 93,500 pixelwise annotated images. The performance of the method has been evaluated using a number of technical metrics, including the Dice metric, mean contour distance and Hausdorff distance, as well as clinically relevant measures, including left ventricle (LV) end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV).

Results

By combining FCN with a large-scale annotated dataset, the proposed automated method achieves a high performance in segmenting the LV and RV on short-axis CMR images and the left atrium (LA) and right atrium (RA) on long-axis CMR images. On a short-axis image test set of 600 subjects, it achieves an average Dice metric of 0.94 for the LV cavity, 0.88 for the LV myocardium and 0.90 for the RV cavity. The mean absolute difference between automated measurement and manual measurement is 6.1 mL for LVEDV, 5.3 mL for LVESV, 6.9 gram for LVM, 8.5 mL for RVEDV and 7.2 mL for RVESV. On long-axis image test sets, the average Dice metric is 0.93 for the LA cavity (2-chamber view), 0.95 for the LA cavity (4-chamber view) and 0.96 for the RA cavity (4-chamber view). The performance is comparable to human inter-observer variability.

Conclusions

We show that an automated method achieves a performance on par with human experts in analysing CMR images and deriving clinically relevant measures.
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Three Distinct Sets of Connector Hubs Integrate Human Brain Function.

Issue 7 Vol 24 Published on 2018-08-01 PMID 30110625 PMCID PMC6886580
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Keywords: fMRI, Functional Connectivity, Brain Networks, Connector Hubs
DOI: https://doi.org/10.1016/j.celrep.2018.07.050
Authors: Evan M Gordon In X Charles J Lynch In X Caterina Gratton In X Timothy O Laumann In X Adrian W Gilmore In X Deanna J Greene In X Mario Ortega In X Annie L Nguyen In X Bradley L Schlaggar In X Steven E Petersen In X Nico U F Dosenbach In X Steven M Nelson In X
Abstract: Control over behavior is enabled by the brain's control networks, which interact with lower-level sensory motor and default networks to regulate their functions. Such interactions are facilitated by specialized "connector hub" regions that interconnect discrete networks. Previous work has treated hubs as a single category of brain regions, although their unitary nature is dubious when examined in individual brains. Here we investigated the nature of hubs by using fMRI to characterize individual-specific hub regions in two independent datasets. We identified three separable sets of connector hubs that integrate information between specific brain networks. These three hub categories occupy different positions within the brain's network structure; they affect networks differently when artificially lesioned, and they are differentially engaged during cognitive and motor task performance. This work suggests a model of brain organization in which different connector hubs integrate control functions and enable top-down control of separate processing streams.
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Bacteriology of the Buttonhole Cannulation Tract in Hemodialysis Patients: A Prospective Cohort Study.

Issue 2 Vol 72 Published on 2018-08-01 PMID 29605379 PMCID N/A
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Keywords: Infection, Staphylococcus aureus, Bacteriology, Staphylococcus epidermidis, Disinfection, hemodialysis, Septicaemia, Bacteraemia, Cannulation, End-stage Renal Disease (Esrd), Needling, Arteriovenous Fistula (Avf), Buttonhole, Access-related Infection
DOI: https://doi.org/10.1053/j.ajkd.2018.01.055
Authors: Line Dahlstrøm Christensen In X Mai-Britt Skadborg In X Agnete H Mortensen In X Carsten Mortensen In X Jens K Møller In X Lars Lemming In X Irene Høgsberg In X Steffen E Petersen In X Niels H Buus In X
Abstract:

Background

The buttonhole cannulation technique for arteriovenous fistulas is widely used, but has been associated with an increased rate of vascular access-related infections. We describe the frequency and type of bacterial colonization of the buttonhole tract over time and associated clinical infections.

Study design

A prospective observational cohort study with 9 months of follow-up.

Setting & participants

84 in-center hemodialysis patients using the buttonhole cannulation technique at 2 Danish dialysis centers.

Outcomes

Bacterial growth from the buttonhole tract and dialysis cannula tip and clinically important infections during follow-up.

Measurements

On 3 occasions 1 month apart, cultures before dialysis (from the skin surrounding the buttonhole before disinfection and from the cannulation tract after disinfection and scab removal) and the cannula tip after dialysis. Patients with positive cultures from the buttonhole tract or cannula tip had repeat cultures within 1 week, along with blood cultures.

Results

Growth from the cannulation tract and/or cannula tip at each of the 3 monthly sets of cultures was found in 18%, 20%, and 17% of patients, respectively. 38% of patients had at least 1 positive culture from the buttonhole tract. Sustained growth was detected in 11% of patients, whereas asymptomatic bacteremia was seen in 30% of those with positive buttonhole cultures. Staphylococci species were the most common pathogens (Staphylococcus aureus, 25%; and Staphylococcus epidermidis, 41%). Colonization-positive buttonholes had more localized redness and slightly more tenderness. During follow-up, significantly more access-related infections were diagnosed among those with positive buttonhole cultures (P<0.001).

Limitations

No comparison to area puncture cannulation technique. Blood cultures were obtained only from patients with positive buttonhole bacteriology.

Conclusions

Transient or sustained colonization of the buttonhole tract by staphylococci and asymptomatic bacteremia is common in hemodialysis patients, implying a substantial risk for access-related infections among patients using a buttonhole cannulation technique. These findings suggest the possible value of surveillance of buttonhole colonization.
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Lifestyle advice and interventions for cardiovascular risk reduction: A systematic review of guidelines.

Issue N/A Vol 263 Published on 2018-07-01 PMID 29754910 PMCID N/A
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Keywords: Systematic review, Guidelines, Lifestyle Advice, Lifestyle Intervention, Cardiovascular Risk Reduction
DOI: https://doi.org/10.1016/j.ijcard.2018.02.094
Authors: Mohammed Y Khanji In X Claudia N van Waardhuizen In X Vinícius V S Bicalho In X Bart S Ferket In X M G Myriam Hunink In X Steffen E Petersen In X
Abstract:

Background

Lifestyle factors are important in preventing cardiovascular disease (CVD) development. We aimed to systematically review guidelines on primary prevention of CVD and their recommendations on lifestyle advice or intervention, in order to guide primary prevention programs.

Methods

Publications in MEDLINE, CINAHL over 7 years since May 3, 2009 were identified. G-I-N International Guideline Library, National Guidelines Clearinghouse, National Library for Health Guideline finder, Canadian Medical Association InfoBase were searched. On the February 8, 2017, we updated the search from Websites of organizations responsible for guidelines development.

Study selection

2 reviewers screened the titles and abstracts to identify Guidelines from Western countries containing recommendations for lifestyle advice and interventions in primary prevention of CVD.

Data extraction

2 reviewers independently assessed rigor of guideline development using the AGREEII instrument, and one extracted recommendations.

Results

Of the 7 guidelines identified, 6 showed good rigor of development (range 45-86%). The guidelines were consistent in recommendations for smoking cessation, limiting saturated fat and salt intake, avoiding transaturated-fat and sugar, with particular emphasis on sugar-sweetened beverages. Guidelines generally agreed on recommendations for physical activity levels and diets rich in fruit, vegetables, fish and wholegrains. Guidelines differed on recommendations for specific dietary patterns and alcohol consumption. Recommendations on psychological factors and sleep are currently limited.

Conclusions

Current guidelines agree on the importance of lifestyle in the prevention of CVD with consensus on most factors including physical activity, smoking cessation and diet, which should be actively integrated in cardiovascular risk reduction programs aiming to improve clinical outcomes.
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Prior fragility fracture and risk of incident ischaemic cardiovascular events: results from UK Biobank.

Issue 6 Vol 29 Published on 2018-06-01 PMID 29479646 PMCID PMC6015763
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Keywords: Heart, Osteoporosis, epidemiology, Fragility Fractures, cardiovascular
DOI: https://doi.org/10.1007/s00198-018-4426-8
Authors: J Paccou In X S D'Angelo In X A Rhodes In X E M Curtis In X Z Raisi-Estabragh In X M Edwards In X K Walker-Bone In X C Cooper In X S E Petersen In X N C Harvey In X
Abstract: In the large UK Biobank population-based cohort, we found that amongst men, but not women, prior fragility fracture was associated with increased risk of admission with ischaemic heart disease.

Introduction

We aimed to investigate the relationship between prior fracture and risk of incident ischaemic cardiovascular events in a UK population-based cohort.

Methods

UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40-69 years, with detailed baseline assessment. History of fracture was self-reported, and details of hospital admissions for ischaemic heart disease (IHD) (ICD-10:I20-I25) were obtained through linkage to UK Hospital Episode Statistics. Cox proportional hazards models were used to investigate the prospective relationships between prior fracture and hospital admission for men and women, controlling for age, BMI, smoking, alcohol, educational level, physical activity, systolic blood pressure, calcium and vitamin D use, ankle spacing-width, heel BUA and HRT use (women).

Results

Amongst men, a fragility fracture (hip, spine, wrist or arm fracture resulting from a simple fall) within the previous 5 years was associated with a 35% increased risk of IHD admission (fully adjusted HR 1.35; 95%CI 1.00, 1.82; p = 0.047), with the relationship predominantly driven by wrist fractures. Associations with hospitalisation for angina in men were similar in age-adjusted models [HR1.54; 95%CI: 1.03, 2.30), p = 0.037], but did not remain statistical significant after full adjustment [HR 1.64; 95%CI: 0.88, 3.07); p = 0.121]. HRs for admission with angina were lower in women, and neither age- nor fully adjusted relationships attained statistical significance.

Conclusions

Prior fragility fracture is an independent risk factor for incident ischaemic cardiovascular events in men. Further work may clarify whether this association is causal or represents shared risk factors, but these findings are likely to be of value in risk assessment of both osteoporosis and cardiovascular disease.
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Behavioral interventions for reducing head motion during MRI scans in children.

Issue N/A Vol 171 Published on 2018-05-01 PMID 29337280 PMCID PMC5857466
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Keywords: Development, Feedback, MRI, Motion, Resting state, Movies
DOI: https://doi.org/10.1016/j.neuroimage.2018.01.023
Authors: Deanna J Greene In X Jonathan M Koller In X Jacqueline M Hampton In X Victoria Wesevich In X Andrew N Van In X Annie L Nguyen In X Catherine R Hoyt In X Lindsey McIntyre In X Eric A Earl In X Rachel L Klein In X Joshua S Shimony In X Steven E Petersen In X Bradley L Schlaggar In X Damien A Fair In X Nico U F Dosenbach In X
Abstract: A major limitation to structural and functional MRI (fMRI) scans is their susceptibility to head motion artifacts. Even submillimeter movements can systematically distort functional connectivity, morphometric, and diffusion imaging results. In patient care, sedation is often used to minimize head motion, but it incurs increased costs and risks. In research settings, sedation is typically not an ethical option. Therefore, safe methods that reduce head motion are critical for improving MRI quality, especially in high movement individuals such as children and neuropsychiatric patients. We investigated the effects of (1) viewing movies and (2) receiving real-time visual feedback about head movement in 24 children (5-15 years old). Children completed fMRI scans during which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and during some of the scans they also received real-time visual feedback about head motion. Head motion was significantly reduced during movie watching compared to rest and when receiving feedback compared to receiving no feedback. However, these results depended on age, such that the effects were largely driven by the younger children. Children older than 10 years showed no significant benefit. We also found that viewing movies significantly altered the functional connectivity of fMRI data, suggesting that fMRI scans during movies cannot be equated to standard resting-state fMRI scans. The implications of these results are twofold: (1) given the reduction in head motion with behavioral interventions, these methods should be tried first for all clinical and structural MRIs in lieu of sedation; and (2) for fMRI research scans, these methods can reduce head motion in certain groups, but investigators must keep in mind the effects on functional MRI data.
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Calcium and Vitamin D Supplementation Are Not Associated With Risk of Incident Ischemic Cardiac Events or Death: Findings From the UK Biobank Cohort.

Open Access Issue 5 Vol 33 Published on 2018-05-01 PMID 29314248 PMCID PMC5915292
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Keywords: Calcium, Vitamin D, Osteoporosis, ischemic heart disease, epidemiology, cardiovascular
DOI: https://doi.org/10.1002/jbmr.3375
Authors: Nicholas C Harvey In X Stefania D'Angelo In X Julien Paccou In X Elizabeth M Curtis In X Mark Edwards In X Zahra Raisi-Estabragh In X Karen Walker-Bone In X Steffen E Petersen In X Cyrus Cooper In X
Abstract: We investigated associations between calcium/vitamin D supplementation and incident cardiovascular events/deaths in a UK population-based cohort. UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40 to 69 years at recruitment. Supplementation with calcium/vitamin D was self-reported, and information on incident hospital admission (ICD-10) for ischemic heart disease (IHD), myocardial infarction (MI), and subsequent death was obtained from linkage to national registers. Cox proportional hazards models were used to investigate longitudinal relationships between calcium/vitamin D supplementation and hospital admission for men/women, controlling for covariates. A total of 475,255 participants (median age 58 years, 55.8% women) had complete data on calcium/vitamin D supplementation. Of that number, 33,437 participants reported taking calcium supplements; 19,089 vitamin D; and 10,007 both. In crude and adjusted analyses, there were no associations between use of calcium supplements and risk of incident hospital admission with either IHD, or subsequent death. Thus, for example, in unadjusted models, the hazard ratio (HR) for admission with myocardial infarction was 0.97 (95% confidence interval [CI] 0.79-1.20, p = 0.79) among women taking calcium supplementation. Corresponding HR for men is 1.16 (95% CI 0.92-1.46, p = 0.22). After full adjustment, HR (95% CI) were 0.82 (0.62-1.07), p = 0.14 among women and 1.12 (0.85-1.48), p = 0.41 among men. Adjusted HR (95% CI) for admission with IHD were 1.05 (0.92-1.19), p = 0.50 among women and 0.97 (0.82-1.15), p = 0.77 among men. Results were similar for vitamin D and combination supplementation. There were no associations with death, and in women, further adjustment for hormone-replacement therapy use did not alter the associations. In this very large prospective cohort, there was no evidence that use of calcium/vitamin D supplementation was associated with increased risk of hospital admission or death after ischemic cardiovascular events. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation.

Issue 2 Vol 98 Published on 2018-04-01 PMID 29673485 PMCID PMC5912345
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Keywords: fMRI, Individual Differences, Functional Connectivity, Brain Networks
DOI: https://doi.org/10.1016/j.neuron.2018.03.035
Authors: Caterina Gratton In X Timothy O Laumann In X Ashley N Nielsen In X Deanna J Greene In X Evan M Gordon In X Adrian W Gilmore In X Steven M Nelson In X Rebecca S Coalson In X Abraham Z Snyder In X Bradley L Schlaggar In X Nico U F Dosenbach In X Steven E Petersen In X
Abstract: The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine.
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Inter-institutional analysis demonstrates the importance of lower than previously anticipated dose regions to prevent late rectal bleeding following prostate radiotherapy.

Issue 1 Vol 127 Published on 2018-04-01 PMID 29530433 PMCID PMC6628908
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Keywords: Toxicity, Radiotherapy, GI, prostate cancer, dose response, Rectal Bleeding
DOI: https://doi.org/10.1016/j.radonc.2018.02.020
Authors: Maria Thor In X Andrew Jackson In X Michael J Zelefsky In X Gunnar Steineck In X Asa Karlsdòttir In X Morten Høyer In X Mitchell Liu In X Nicola J Nasser In X Stine E Petersen In X Vitali Moiseenko In X Joseph O Deasy In X
Abstract:

Purpose

To investigate whether inter-institutional cohort analysis uncovers more reliable dose-response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy.

Material and methods

Data from five institutions were used. Rectal dose-volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70-86.4 Gy@1.8-2.0 Gy/fraction were obtained, and corrected for fractionation effects (α/β = 3 Gy). Cohorts with best-fit Lyman-Kutcher-Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose-response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability.

Results

Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer-Lemeshow p-value, pHL = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; pHL = 0.63), indicating a logistically shaped dose-response.

Conclusion

We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose-volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy.
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Diagnosing coronary artery disease after a positive coronary computed tomography angiography: the Dan-NICAD open label, parallel, head to head, randomized controlled diagnostic accuracy trial of cardiovascular magnetic resonance and myocardial perfusion scintigraphy.

Issue 4 Vol 19 Published on 2018-04-01 PMID 29447342 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jex342
Authors: L Nissen In X S Winther In X J Westra In X J A Ejlersen In X C Isaksen In X A Rossi In X N R Holm In X G Urbonaviciene In X L C Gormsen In X L H Madsen In X E H Christiansen In X M Maeng In X L L Knudsen In X L Frost In X L Brix In X H E Bøtker In X S E Petersen In X M Bøttcher In X
Abstract:

Aims

Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA.

Methods and results

Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively.

Conclusion

Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.
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Re-emergence of modular brain networks in stroke recovery.

Issue N/A Vol 101 Published on 2018-04-01 PMID 29414460 PMCID PMC6527102
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Keywords: Memory, Recovery, Language, Stroke, Functional Connectivity
DOI: https://doi.org/10.1016/j.cortex.2017.12.019
Authors: Joshua S Siegel In X Benjamin A Seitzman In X Lenny E Ramsey In X Mario Ortega In X Evan M Gordon In X Nico U F Dosenbach In X Steven E Petersen In X Gordon L Shulman In X Maurizio Corbetta In X
Abstract: Studies of stroke have identified local reorganization in perilesional tissue. However, because the brain is highly networked, strokes also broadly alter the brain's global network organization. Here, we assess brain network structure longitudinally in adult stroke patients using resting state fMRI. The topology and boundaries of cortical regions remain grossly unchanged across recovery. In contrast, the modularity of brain systems i.e. the degree of integration within and segregation between networks, was significantly reduced sub-acutely (n = 107), but partially recovered by 3 months (n = 85), and 1 year (n = 67). Importantly, network recovery correlated with recovery from language, spatial memory, and attention deficits, but not motor or visual deficits. Finally, in-depth single subject analyses were conducted using tools for visualization of changes in brain networks over time. This exploration indicated that changes in modularity during successful recovery reflect specific alterations in the relationships between different networks. For example, in a patient with left temporo-parietal stroke and severe aphasia, sub-acute loss of modularity reflected loss of association between frontal and temporo-parietal regions bi-hemispherically across multiple modules. These long-distance connections then returned over time, paralleling aphasia recovery. This work establishes the potential importance of normalization of large-scale modular brain systems in stroke recovery.
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Control networks and hubs.

Issue 3 Vol 55 Published on 2018-03-01 PMID 29193146 PMCID PMC5811327
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Keywords: fMRI, Networks, Cognitive Control, Functional Connectivity, Executive Control
DOI: https://doi.org/10.1111/psyp.13032
Authors: Caterina Gratton In X Haoxin Sun In X Steven E Petersen In X
Abstract: Executive control functions are associated with frontal, parietal, cingulate, and insular brain regions that interact through distributed large-scale networks. Here, we discuss how fMRI functional connectivity can shed light on the organization of control networks and how they interact with other parts of the brain. In the first section of our review, we present convergent evidence from fMRI functional connectivity, activation, and lesion studies that there are multiple dissociable control networks in the brain with distinct functional properties. In the second section, we discuss how graph theoretical concepts can help illuminate the mechanisms by which control networks interact with other brain regions to carry out goal-directed functions, focusing on the role of specialized hub regions for mediating cross-network interactions. Again, we use a combination of functional connectivity, lesion, and task activation studies to bolster this claim. We conclude that a large-scale network perspective provides important neurobiological constraints on the neural underpinnings of executive control, which will guide future basic and translational research into executive function and its disruption in disease.
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Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy.

Issue 4 Vol 91 Published on 2018-03-01 PMID 28766836 PMCID N/A
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Keywords: Doppler echocardiography, hypertrophic cardiomyopathy, Obstruction, Mid-cavity
DOI: https://doi.org/10.1002/ccd.27143
Authors: James W Malcolmson In X Stephen M Hamshere In X Abhishek Joshi In X Constantinos O'Mahony In X Mehul Dhinoja In X Steffen E Petersen In X Neha Sekhri In X Saidi A Mohiddin In X
Abstract:

Objectives

To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM).

Background

LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction.

Methods

Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS).

Results

Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively. Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies.

Conclusions

Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM.
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Fully-automated left ventricular mass and volume MRI analysis in the UK Biobank population cohort: evaluation of initial results.

Open Access Issue 2 Vol 34 Published on 2018-02-01 PMID 28836039 PMCID PMC5809564
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Keywords: Automated analysis, Ventricular function, Uk Biobank
DOI: https://doi.org/10.1007/s10554-017-1225-9
Authors: Avan Suinesiaputra In X Mihir M Sanghvi In X Nay Aung In X Jose Miguel Paiva In X Filip Zemrak In X Kenneth Fung In X Elena Lukaschuk In X Aaron M Lee In X Valentina Carapella In X Young Jin Kim In X Jane Francis In X Stefan K Piechnik In X Stefan Neubauer In X Andreas Greiser In X Marie-Pierre Jolly In X Carmel Hayes In X Alistair A Young In X Steffen E Petersen In X
Abstract: UK Biobank, a large cohort study, plans to acquire 100,000 cardiac MRI studies by 2020. Although fully-automated left ventricular (LV) analysis was performed in the original acquisition, this was not designed for unsupervised incorporation into epidemiological studies. We sought to evaluate automated LV mass and volume (Siemens syngo InlineVF versions D13A and E11C), against manual analysis in a substantial sub-cohort of UK Biobank participants. Eight readers from two centers, trained to give consistent results, manually analyzed 4874 UK Biobank cases for LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass (LVM). Agreement between manual and InlineVF automated analyses were evaluated using Bland-Altman analysis and the intra-class correlation coefficient (ICC). Tenfold cross-validation was used to establish a linear regression calibration between manual and InlineVF results. InlineVF D13A returned results in 4423 cases, whereas InlineVF E11C returned results in 4775 cases and also reported LVM. Rapid visual assessment of the E11C results found 178 cases (3.7%) with grossly misplaced contours or landmarks. In the remaining 4597 cases, LV function showed good agreement: ESV -6.4 ± 9.0 ml, 0.853 (mean ± SD of the differences, ICC) EDV -3.0 ± 11.6 ml, 0.937; SV 3.4 ± 9.8 ml, 0.855; and EF 3.5 ± 5.1%, 0.586. Although LV mass was consistently overestimated (29.9 ± 17.0 g, 0.534) due to larger epicardial contours on all slices, linear regression could be used to correct the bias and improve accuracy. Automated InlineVF results can be used for case-control studies in UK Biobank, provided visual quality control and linear bias correction are performed. Improvements between InlineVF D13A and InlineVF E11C show the field is rapidly advancing, with further improvements expected in the near future.
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Cortical Functional Connectivity Evident After Birth and Behavioral Inhibition at Age 2.

Issue 2 Vol 175 Published on 2018-02-01 PMID 28774192 PMCID PMC5794627
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Keywords: Infant, Anxiety, biological markers, Default Mode Network, Behavioral Inhibition, Ventral Attention Network
DOI: https://doi.org/10.1176/appi.ajp.2017.17010018
Authors: Chad M Sylvester In X Christopher D Smyser In X Tara Smyser In X Jeanette Kenley In X Joseph J Ackerman In X Joshua S Shimony In X Steve E Petersen In X Cynthia E Rogers In X
Abstract:

Objective

The infant temperament behavioral inhibition is a potent risk factor for development of an anxiety disorder. It is difficult to predict risk for behavioral inhibition at birth, however, and the neural underpinnings are poorly understood. The authors hypothesized that neonatal functional connectivity of the ventral attention network is related to behavioral inhibition at age 2 years beyond sociodemographic and familial factors. This hypothesis is supported by the ventral attention network's role in attention to novelty, a key feature of behavioral inhibition.

Method

Using a longitudinal design (N=45), the authors measured functional connectivity using MRI in neonates and behavioral inhibition at age 2 using the Infant-Toddler Social and Emotional Assessment. Whole-brain connectivity maps were computed for regions from the ventral attention, default mode, and salience networks. Regression analyses related these maps to behavioral inhibition at age 2, covarying for sex, social risk, and motion during scanning.

Results

Decreased neonatal functional connectivity of three connections was associated with increased behavioral inhibition at age 2. One connection (between the right ventrolateral prefrontal cortex and the right temporal-parietal junction) included the ventral attention network seed, and two connections (between the medial prefrontal cortex and both the right superior parietal lobule and the left lateral occipital cortex) included the default mode network seed.

Conclusions

Neonatal functional connectivity of the ventral attention and default mode networks is associated with behavioral inhibition at age 2. These results inform the developmental neurobiology of behavioral inhibition and anxiety disorders and may aid in early risk assessment and intervention.
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Variation in lung function and alterations in cardiac structure and function-Analysis of the UK Biobank cardiovascular magnetic resonance imaging substudy.

Open Access Issue 3 Vol 13 Published on 2018-01-01 PMID 29558496 PMCID PMC5860758
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0194434
Authors: Ross J Thomson In X Nay Aung In X Mihir M Sanghvi In X Jose Miguel Paiva In X Aaron M Lee In X Filip Zemrak In X Kenneth Fung In X Paul E Pfeffer In X Alexander J Mackay In X Tricia M McKeever In X Elena Lukaschuk In X Valentina Carapella In X Young Jin Kim In X Charlotte E Bolton In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Reduced lung function is common and associated with increased cardiovascular morbidity and mortality, even in asymptomatic individuals without diagnosed respiratory disease. Previous studies have identified relationships between lung function and cardiovascular structure in individuals with pulmonary disease, but the relationships in those free from diagnosed cardiorespiratory disease have not been fully explored.

Methods

UK Biobank is a prospective cohort study of community participants in the United Kingdom. Individuals self-reported demographics and co-morbidities, and a subset underwent cardiovascular magnetic resonance (CMR) imaging and spirometry. CMR images were analysed to derive ventricular volumes and mass. The relationships between CMR-derived measures and spirometry and age were modelled with multivariable linear regression, taking account of the effects of possible confounders.

Results

Data were available for 4,975 individuals, and after exclusion of those with pre-existing cardiorespiratory disease and unacceptable spirometry, 1,406 were included in the analyses. In fully-adjusted multivariable linear models lower FEV1 and FVC were associated with smaller left ventricular end-diastolic (-5.21ml per standard deviation (SD) change in FEV1, -5.69ml per SD change in FVC), end-systolic (-2.34ml, -2.56ml) and stroke volumes (-2.85ml, -3.11ml); right ventricular end-diastolic (-5.62ml, -5.84ml), end-systolic (-2.47ml, -2.46ml) and stroke volumes (-3.13ml, -3.36ml); and with lower left ventricular mass (-2.29g, -2.46g). Changes of comparable magnitude and direction were observed per decade increase in age.

Conclusions

This study shows that reduced FEV1 and FVC are associated with smaller ventricular volumes and reduced ventricular mass. The changes seen per standard deviation change in FEV1 and FVC are comparable to one decade of ageing.
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Prospective association between handgrip strength and cardiac structure and function in UK adults.

Open Access Issue 3 Vol 13 Published on 2018-01-01 PMID 29538386 PMCID PMC5851546
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0193124
Authors: Sebastian E Beyer In X Mihir M Sanghvi In X Nay Aung In X Alice Hosking In X Jackie A Cooper In X José Miguel Paiva In X Aaron M Lee In X Kenneth Fung In X Elena Lukaschuk In X Valentina Carapella In X Murray A Mittleman In X Soren Brage In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Handgrip strength, a measure of muscular fitness, is associated with cardiovascular (CV) events and CV mortality but its association with cardiac structure and function is unknown. The goal of this study was to determine if handgrip strength is associated with changes in cardiac structure and function in UK adults.

Methods and results

Left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), mass (M), and mass-to-volume ratio (MVR) were measured in a sample of 4,654 participants of the UK Biobank Study 6.3 ± 1 years after baseline using cardiovascular magnetic resonance (CMR). Handgrip strength was measured at baseline and at the imaging follow-up examination. We determined the association between handgrip strength at baseline as well as its change over time and each of the cardiac outcome parameters. After adjustment, higher level of handgrip strength at baseline was associated with higher LVEDV (difference per SD increase in handgrip strength: 1.3ml, 95% CI 0.1-2.4; p = 0.034), higher LVSV (1.0ml, 0.3-1.8; p = 0.006), lower LVM (-1.0g, -1.8 --0.3; p = 0.007), and lower LVMVR (-0.013g/ml, -0.018 --0.007; p<0.001). The association between handgrip strength and LVEDV and LVSV was strongest among younger individuals, while the association with LVM and LVMVR was strongest among older individuals.

Conclusions

Better handgrip strength was associated with cardiac structure and function in a pattern indicative of less cardiac hypertrophy and remodeling. These characteristics are known to be associated with a lower risk of cardiovascular events.
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The impact of menopausal hormone therapy (MHT) on cardiac structure and function: Insights from the UK Biobank imaging enhancement study.

Open Access Issue 3 Vol 13 Published on 2018-01-01 PMID 29518141 PMCID PMC5843282
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0194015
Authors: Mihir M Sanghvi In X Nay Aung In X Jackie A Cooper In X José Miguel Paiva In X Aaron M Lee In X Filip Zemrak In X Kenneth Fung In X Ross J Thomson In X Elena Lukaschuk In X Valentina Carapella In X Young Jin Kim In X Nicholas C Harvey In X Stefan K Piechnik In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

The effect of menopausal hormone therapy (MHT)-previously known as hormone replacement therapy-on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort.

Methods

Post-menopausal women who had never used MHT and those who had used MHT ≥3 years participating in the UK Biobank who had undergone cardiovascular magnetic resonance (CMR) imaging and free of known cardiovascular disease were included. Multivariable linear regression was performed to examine the relationship between cardiac parameters and MHT use ≥3 years. To explore whether MHT use on each of the cardiac outcomes differed by age, multivariable regression models were constructed with a cross-product of age and MHT fitted as an interaction term.

Results

Of 1604 post-menopausal women, 513 (32%) had used MHT ≥3 years. In the MHT cohort, median age at menopause was 50 (IQR: 45-52) and median duration of MHT was 8 years. In the non-MHT cohort, median age at menopause was 51 (IQR: 48-53). MHT use was associated with significantly lower LV end-diastolic volume (122.8 ml vs 119.8 ml, effect size = -2.4%, 95% CI: -4.2% to -0.5%; p = 0.013) and LA maximal volume (60.2 ml vs 57.5 ml, effect size = -4.5%, 95% CI: -7.8% to -1.0%; p = 0.012). There was no significant difference in LV mass. MHT use significantly modified the effect between age and CMR parameters; MHT users had greater decrements in LV end-diastolic volume, LV end-systolic volume and LA maximal volume with advancing age.

Conclusions

MHT use was not associated with adverse, subclinical changes in cardiac structure and function. Indeed, significantly smaller LV and LA chamber volumes were observed which have been linked to favourable cardiovascular outcomes. These findings represent a novel approach to examining MHT's effect on the cardiovascular system.
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Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

Issue N/A Vol 251 Published on 2018-01-01 PMID 29197461 PMCID N/A
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Keywords: Perfusion, hypertrophic cardiomyopathy, Cmr, Cardiac Magnetic Resonance
DOI: https://doi.org/10.1016/j.ijcard.2017.09.206
Authors: Edward Stephenson In X Pierre Monney In X Francesca Pugliese In X James Malcolmson In X Steffen E Petersen In X Charles Knight In X Peter Mills In X Andrew Wragg In X Constantinos O'Mahony In X Neha Sekhri In X Saidi A Mohiddin In X
Abstract:

Objectives

To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain.

Background

Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain.

Methods

We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV).

Results

In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001).

Conclusion

In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output.
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Amygdala Reward Reactivity Mediates the Association Between Preschool Stress Response and Depression Severity.

Issue 2 Vol 83 Published on 2018-01-01 PMID 29102026 PMCID PMC5723551
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Keywords: Development, Stress, Amygdala, fMRI, Depression, Reward Processing
DOI: https://doi.org/10.1016/j.biopsych.2017.08.020
Authors: Michael S Gaffrey In X Deanna M Barch In X Ryan Bogdan In X Katrina Farris In X Steven E Petersen In X Joan L Luby In X
Abstract:

Background

Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old.

Methods

Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured.

Results

Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity.

Conclusions

Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression.
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Diagnosis and Prognosis in Sudden Cardiac Arrest Survivors Without Coronary Artery Disease: Utility of a Clinical Approach Using Cardiac Magnetic Resonance Imaging.

Issue 12 Vol 10 Published on 2017-12-01 PMID 29237609 PMCID N/A
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Keywords: Prognosis, Magnetic Resonance Imaging, coronary artery disease, Heart Arrest, Arrhythmias, Cardiac, Death, Sudden, Cardiac
DOI: https://doi.org/10.1161/circimaging.117.006709
Authors: Patricia Rodrigues In X Abhishek Joshi In X Howell Williams In X Mark Westwood In X Steffen E Petersen In X Filip Zemrak In X Richard J Schilling In X Claire Kirkby In X Andrew Wragg In X Charlotte Manisty In X Saidi Mohiddin In X
Abstract:

Background

Determining the pathogenesis of sudden cardiac arrest or periarrest without significant coronary artery disease is crucial for management and prognosis. Cardiovascular magnetic resonance (CMR) can detect morphological, functional, or tissue abnormalities, and we sought to evaluate the role of CMR in determining sudden cardiac arrest pathogenesis and prognosis in survivors.

Methods and results

We retrospectively reviewed cardiac investigations and clinical outcomes in consecutive survivors of potentially fatal arrhythmias without coronary artery disease admitted to our institutions from 2008 to 2014. After coronary angiography and echocardiography, all underwent CMR and, when indicated, electrophysiology studies. Major adverse cardiac events (MACE), comprising significant nonfatal ventricular arrhythmia or death, was the primary outcome. Of 164 included subjects (65% men; mean age 48 [18-80] years), CMR contributed to the diagnosis in 80 (49%) and was decisive in 50 cases (30%). Dilated cardiomyopathy (n=27), myocarditis or sarcoidosis (n=22), occult myocardial infarction (n=13), and hypertrophic cardiomyopathy (n=9) were most frequent. Arrhythmic causes were found in 14% while no cause was identified in 36%. MACE occurred in 31% of subjects during a median follow-up of 32 months. MACE associated with presence of a CMR diagnosis, extent of late gadolinium enhancement, and left and right ventricular ejection fractions. Right ventricular ejection fraction was an independent predictor of MACE.

Conclusions

CMR identified a likely pathogenesis for sudden cardiac arrest in nearly half of survivors in whom coronary artery disease had been excluded. One in 3 subjects had MACE; risk doubled in those with a CMR diagnosis and some CMR parameters-late gadolinium enhancement, left ventricular ejection fraction, and especially right ventricular ejection fraction-associated with prognosis.
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On Global fMRI Signals and Simulations.

Issue 12 Vol 21 Published on 2017-12-01 PMID 28939332 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.tics.2017.09.002
Authors: Jonathan D Power In X Timothy O Laumann In X Mark Plitt In X Alex Martin In X Steven E Petersen In X
Abstract: No Abstract Available
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Myocardial deformation assessment using cardiovascular magnetic resonance-feature tracking technique.

Issue 1080 Vol 90 Published on 2017-12-01 PMID 28830199 PMCID PMC6047663
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Keywords:
DOI: https://doi.org/10.1259/bjr.20170072
Authors: Haifa M Almutairi In X Redha Boubertakh In X Marc E Miquel In X Steffen E Petersen In X
Abstract:

Background

Cardiovascular magnetic resonance (CMR) imaging is an important modality that allows the assessment of regional myocardial function by measuring myocardial deformation parameters, such as strain and strain rate throughout the cardiac cycle. Feature tracking is a promising quantitative post-processing technique that is increasingly used. It is commonly applied to cine images, in particular steady-state free precession, acquired during routine CMR examinations.

Objective

To review the studies that have used feature tracking techniques in healthy subjects or patients with cardiovascular diseases. The article emphasizes the advantages and limitations of feature tracking when applied to regional deformation parameters. The challenges of applying the techniques in clinics and potential solutions are also reviewed.

Results

Research studies in healthy volunteers and/or patients either applied CMR-feature tracking alone to assess myocardial motion or compared it with either established CMR-tagging techniques or to speckle tracking echocardiography. These studies assessed the feasibility and reliability of calculating or determining global and regional myocardial deformation strain parameters. Regional deformation parameters are reviewed and compared. Better reproducibility for global deformation was observed compared with segmental parameters. Overall, studies demonstrated that circumferential was the most reproducible deformation parameter, usually followed by longitudinal strain; in contrast, radial strain showed high variability.

Conclusion

Although feature tracking is a promising tool, there are still discrepancies in the results obtained using different software packages. This highlights a clear need for standardization of MRI acquisition parameters and feature tracking analysis methodologies. Validation, including physical and numerical phantoms, is still required to facilitate the use of feature tracking in routine clinical practice.
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Late urinary morbidity and quality of life after radical prostatectomy and salvage radiotherapy for prostate cancer.

Issue 6 Vol 51 Published on 2017-12-01 PMID 28748716 PMCID N/A
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Keywords: Prostatic neoplasms, Radiotherapy, Quality of life, Prostatectomy, Lower Urinary Tract Symptoms, Patient-reported Outcome, Late Morbidity
DOI: https://doi.org/10.1080/21681805.2017.1354314
Authors: Maria Ervandian In X Morten Høyer In X Stine Elleberg Petersen In X Lisa Sengeløv In X Steinbjørn Hansen In X Mette Moe Kempel In X Peter Meidahl Petersen In X Michael Borre In X
Abstract:

Objective

There is a paucity of knowledge of long-term urinary morbidity in patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and salvage radiotherapy (SRT). Improved long-term survival calls for heightened awareness of late effects from radiotherapy after RP. The purpose of this study was to assess late urinary morbidity and its potential impact on quality of life (QoL) in patients treated with RP plus SRT compared with patients treated with RP alone.

Materials and methods

Long-term morbidity and QoL were evaluated using a cross-sectional design with validated questionnaires in urinary morbidity [Danish Prostatic Symptom Score (DAN-PSS)] and QoL [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)]. Included were a total of 227 patients treated with SRT and 192 treated with RP in the periods 2006-2010 and 2005-2007, respectively.

Results

Weak stream, straining, frequency and nocturia were significantly more prevalent in patients treated with RP + SRT than in patients treated with RP alone. Patients treated with RP + SRT generally suffered from more severe urinary symptoms. The QoL scores of the two treatment groups were not statistically significantly different, but a high level of urinary morbidity was significantly related to decreased QoL (p = 0.000).

Conclusions

Patients treated with SRT have a higher rate of urinary morbidity than do patients treated with RP alone. Severe urinary morbidity was significantly related to decreased QoL, but did not differ between the two treatment groups.
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Protocol and quality assurance for carotid imaging in 100,000 participants of UK Biobank: development and assessment.

Issue 17 Vol 24 Published on 2017-11-01 PMID 28925747 PMCID N/A
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Keywords: Quality assurance, ultrasound, Carotid intima-media thickness, Carotid, Carotid Imt, Uk Biobank
DOI: https://doi.org/10.1177/2047487317732273
Authors: Sean Coffey In X Adam J Lewandowski In X Steve Garratt In X Rudy Meijer In X Steven Lynum In X Ram Bedi In X James Paterson In X Mohammad Yaqub In X J Alison Noble In X Stefan Neubauer In X Steffen E Petersen In X Naomi Allen In X Cathie Sudlow In X Rory Collins In X Paul M Matthews In X Paul Leeson In X
Abstract: Background Ultrasound imaging is able to quantify carotid arterial wall structure for the assessment of cerebral and cardiovascular disease risks. We describe a protocol and quality assurance process to enable carotid imaging at large scale that has been developed for the UK Biobank Imaging Enhancement Study of 100,000 individuals. Design An imaging protocol was developed to allow measurement of carotid intima-media thickness from the far wall of both common carotid arteries. Six quality assurance criteria were defined and a web-based interface (Intelligent Ultrasound) was developed to facilitate rapid assessment of images against each criterion. Results and conclusions Excellent inter and intra-observer agreements were obtained for image quality evaluations on a test dataset from 100 individuals. The image quality criteria then were applied in the UK Biobank Imaging Enhancement Study. Data from 2560 participants were evaluated. Feedback of results to the imaging team led to improvement in quality assurance, with quality assurance failures falling from 16.2% in the first two-month period examined to 6.4% in the last. Eighty per cent had all carotid intima-media thickness images graded as of acceptable quality, with at least one image acceptable for 98% of participants. Carotid intima-media thickness measures showed expected associations with increasing age and gender. Carotid imaging can be performed consistently, with semi-automated quality assurance of all scans, in a limited timeframe within a large scale multimodality imaging assessment. Routine feedback of quality control metrics to operators can improve the quality of the data collection.
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Spatial rectal dose/volume metrics predict patient-reported gastro-intestinal symptoms after radiotherapy for prostate cancer.

Issue 11 Vol 56 Published on 2017-11-01 PMID 28885095 PMCID PMC6619498
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Keywords:
DOI: https://doi.org/10.1080/0284186x.2017.1370130
Authors: Oscar Casares-Magaz In X Ludvig Paul Muren In X Vitali Moiseenko In X Stine E Petersen In X Niclas Johan Pettersson In X Morten Høyer In X Joseph O Deasy In X Maria Thor In X
Abstract:

Background

Gastro-intestinal (GI) toxicity after radiotherapy (RT) for prostate cancer reduces patient's quality of life. In this study, we explored associations between spatial rectal dose/volume metrics and patient-reported GI symptoms after RT for localized prostate cancer, and compared these with those of dose-surface/volume histogram (DSH/DVH) metrics.

Material and methods

Dose distributions and six GI symptoms (defecation urgency/emptying difficulties/fecal leakage, ≥Grade 2, median follow-up: 3.6 y) were extracted for 200 patients treated with image-guided RT in 2005-2007. Three hundred and nine metrics assessed from 2D rectal dose maps or DSHs/DVHs were subject to 50-times iterated five-fold cross-validated univariate and multivariate logistic regression analysis (UVA, MVA). Performance of the most frequently selected MVA models was evaluated by the area under the receiving-operating characteristics curve (AUC).

Results

The AUC increased for dose-map compared to DSH/DVH-based models (mean SD: 0.64 ± 0.03 vs. 0.61 ± 0.01), and significant relations were found for six versus four symptoms. Defecation urgency and faecal leakage were explained by high doses at the central/upper and central areas, respectively; while emptying difficulties were explained by longitudinal extensions of intermediate doses.

Conclusions

Predictability of patient-reported GI toxicity increased using spatial metrics compared to DSH/DVH metrics. Novel associations were particularly identified for emptying difficulties using both approaches in which intermediate doses were emphasized.
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Validation of genetic predictors of late radiation-induced morbidity in prostate cancer patients.

Issue 11 Vol 56 Published on 2017-11-01 PMID 28844157 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1080/0284186x.2017.1348626
Authors: Line M H Schack In X Stine E Petersen In X Steffen Nielsen In X Lilly Lundby In X Morten Høyer In X Lise Bentzen In X Jens Overgaard In X Christian N Andreassen In X Jan Alsner In X
Abstract:

Introduction

Normal tissue morbidity sets the dose limit for radiotherapy (RT) in cancer treatment and has importance for quality of life for cancer survivors. A previous study of prostate cancer patients treated with RT generated clinical data for radiation-induced morbidity measured by anorectal physiological methods and validated questionnaires. Other studies have identified genetic predictors associated with late radiation-induced morbidity outcome. We have expanded biobank material aiming to validate single nucleotide polymorphisms (SNPs) and a gene expression classifier with endpoints on patient-reported outcomes and biomechanical properties of the anorectum from our cohort matching originally published endpoints.

Materials and methods

The present cohort of prostate cancer patients was treated with RT curative intent in 1999-2007. Nine SNPs associated with late radiation-induced morbidity were tested in 96 patients (rs2788612, rs1800629, rs264663, rs2682585, rs2268363, rs1801516, rs13035033, rs7120482 and rs17779457). A validated gene expression profile predictive of resistance to radiation-induced skin fibrosis was tested in 42 patients. An RT-induced anorectal dysfunction score (RT-ARD) served as a fibrosis-surrogate and a measure of overall radiation-induced morbidity.

Results

The lowest p-value found in the genotype analyses was for SNP rs2682585 minor allele (A) in the FSHR gene and the RT-ARD score with odds ratios (OR) = 1.76; 95% CI (0.98-3.17) p = .06, which was out of concordance with original data showing a protective effect of the minor allele. The gene expression profile in patients classified as fibrosis-resistant was associated with high RT-ARD scores OR 4.18; 95% CI (1.1-16.6), p = .04 conflicting with the hypothesis that fibrosis-resistant patients would experience lower RT-ARD scores.

Conclusions

We aimed to validate nine SNPs and a gene expression classifier in a cohort of prostate cancer patients with unique scoring of radiation-induced morbidity. One significant association was found, pointing to the opposite direction of originally published data. We conclude that the material was not able to validate previously published genetic predictors of radiation-induced morbidity.
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Evaluation of splenic switch off in a tertiary imaging centre: validation and assessment of utility.

Issue 11 Vol 18 Published on 2017-11-01 PMID 28329392 PMCID N/A
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Keywords: Adenosine, Cardiac Magnetic Resonance, Splenic Switch-off, Stress Cmr
DOI: https://doi.org/10.1093/ehjci/jew205
Authors: Alice Hosking In X Marinos Koulouroudias In X Filip Zemrak In X James C Moon In X Alexia Rossi In X Aaron Lee In X Michael R Barnes In X Redha Boubertakh In X Francesca Pugliese In X Charlotte Manisty In X Steffen E Petersen In X
Abstract:

Aims

Adenosine can induce splenic vasoconstriction (splenic switch-off, SSO). In this study, we aim to evaluate the utility of identifying a lack of SSO for detecting false-negative adenosine stress perfusion cardiac magnetic resonance (CMR) scans.

Methods and results

We visually analysed 492 adenosine stress perfusion CMR scans reported as negative in a cohort of patients with no previous history of coronary artery disease. A lack of SSO was identified in 11%. We quantified the phenomenon by drawing regions of interest on the spleen and comparing intensity between stress and rest scans, the spleen intensity ratio (SIR). Inter-rater agreement for qualitative determination of SSO was κ = 0.81 and inter-class correlation for quantitative determination of SSO was 0.94. The optimal threshold for SIR as an indicator of SSO was 0.40 (sensitivity = 82.5%, specificity = 92.3%, AUC = 0.91). 23 065 CMR scans and 9926 invasive coronary angiogram reports were retrospectively examined to identify patients with negative CMR scans who required coronary intervention in the subsequent 12 months (false negatives). We compared these scans with true positives who had positive adenosine stress perfusion CMR scans followed by coronary intervention. The rate of lack of SSO was 20.7% in the false-negative group versus 13.1% in true positives (P = 0.37).

Conclusion

The lack of SSO is prevalent, easily measureable, and has potential to improve on haemodynamic criteria as a marker of adenosine understress in CMR perfusion scans.
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Multimodality Imaging in Restrictive Cardiomyopathies: An EACVI expert consensus document In collaboration with the "Working Group on myocardial and pericardial diseases" of the European Society of Cardiology Endorsed by The Indian Academy of Echocardiography.

Issue 10 Vol 18 Published on 2017-10-01 PMID 28510718 PMCID N/A
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Keywords: Echocardiography, computed tomography, Nuclear Imaging, Cardiomyopathies, Cardiac Magnetic Resonance, Restrictive Cardiomyopathies
DOI: https://doi.org/10.1093/ehjci/jex034
Authors: Gilbert Habib In X Chiara Bucciarelli-Ducci In X Alida L P Caforio In X Nuno Cardim In X Philippe Charron In X Bernard Cosyns In X Aurélie Dehaene In X Genevieve Derumeaux In X Erwan Donal In X Marc R Dweck In X Thor Edvardsen In X Paola Anna Erba In X Laura Ernande In X Oliver Gaemperli In X Maurizio Galderisi In X Julia Grapsa In X Alexis Jacquier In X Karin Klingel In X Patrizio Lancellotti In X Danilo Neglia In X Alessia Pepe In X Pasquale Perrone-Filardi In X Steffen E Petersen In X Sven Plein In X Bogdan A Popescu In X Patricia Reant In X L Elif Sade In X Erwan Salaun In X Riemer H J A Slart In X Christophe Tribouilloy In X Jose Zamorano In X In X In X
Abstract: Restrictive cardiomyopathies (RCMs) are a diverse group of myocardial diseases with a wide range of aetiologies, including familial, genetic and acquired diseases and ranging from very rare to relatively frequent cardiac disorders. In all these diseases, imaging techniques play a central role. Advanced imaging techniques provide important novel data on the diagnostic and prognostic assessment of RCMs. This EACVI consensus document provides comprehensive information for the appropriateness of all non-invasive imaging techniques for the diagnosis, prognostic evaluation, and management of patients with RCM.
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Community delivery of semiautomated fractal analysis tool in cardiac mr for trabecular phenotyping.

Issue 4 Vol 46 Published on 2017-10-01 PMID 28152235 PMCID N/A
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Keywords: Structure, Etiology, MRI, Diagnostic Testing, Myocardial Cardiomyopathy Disease, Myocardial Biology
DOI: https://doi.org/10.1002/jmri.25644
Authors: Gabriella Captur In X Dina Radenkovic In X Chunming Li In X Yu Liu In X Nay Aung In X Filip Zemrak In X Catalina Tobon-Gomez In X Xuexin Gao In X Perry M Elliott In X Steffen E Petersen In X David A Bluemke In X Matthias G Friedrich In X James C Moon In X
Abstract:

Purpose

To report the development of easy-to-use magnetic resonance imaging (MRI) fractal tools deployed on platforms accessible to all. The trabeculae of the left ventricle vary in health and disease but their measurement is difficult. Fractal analysis of cardiac MR images can measure trabecular complexity as a fractal dimension (FD).

Materials and methods

This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the local Institutional Review Board. Participants provided written informed consent. The original MatLab implementation (region-based level set segmentation and box-counting algorithm) was recoded for two platforms (OsiriX and a clinical MR reporting platform [cvi42 , Circle Cardiovascular Imaging, Calgary, Canada]). For validation, 100 subjects were scanned at 1.5T and 20 imaged twice for interstudy reproducibility. Cines were analyzed by the three tools and FD variability determined. Manual trabecular delineation by an expert reader (R1) provided ground truth contours for validation of segmentation accuracy by point-to-curve (P2C) distance estimates. Manual delineation was repeated by R1 and a second reader (R2) on 15 cases for intra/interobserver variability.

Results

FD by OsiriX and the clinical MR reporting platform showed high correlation with MatLab values (correlation coefficients: 0.96 [95% CI: 0.95-0.97] and 0.96 [0.95-0.96]) and high interstudy and intraplatform reproducibility. Semiautomated contours in OsiriX and the clinical MR reporting platform were highly correlated with ground truth contours evidenced by low P2C errors: 0.882 ± 0.76 mm and 0.709 ± 0.617 mm. Validity of ground truth contours was inferred from low P2C errors between readers (R1-R1: 0.798 ± 0.718 mm; R1-R2: 0.804 ± 0.649 mm).

Conclusion

This set of accessible fractal tools that measure trabeculation in the heart have been validated and released to the cardiac MR community (http://j.mp/29xOw3B) to encourage novel clinical applications of fractals in the cardiac imaging domain.

Level of evidence

3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1082-1088.
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On the Stability of BOLD fMRI Correlations.

Issue 10 Vol 27 Published on 2017-10-01 PMID 27591147 PMCID PMC6248456
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Keywords: Dynamics, Resting state, Functional Connectivity, Bold Fmri, Nonstationarity
DOI: https://doi.org/10.1093/cercor/bhw265
Authors: Timothy O Laumann In X Abraham Z Snyder In X Anish Mitra In X Evan M Gordon In X Caterina Gratton In X Babatunde Adeyemo In X Adrian W Gilmore In X Steven M Nelson In X Jeff J Berg In X Deanna J Greene In X John E McCarthy In X Enzo Tagliazucchi In X Helmut Laufs In X Bradley L Schlaggar In X Nico U F Dosenbach In X Steven E Petersen In X
Abstract: Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.
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Excessive Trabeculations and Prognosis: The Plot Thickens.

Issue 9 Vol 10 Published on 2017-09-01 PMID 28899952 PMCID N/A
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Keywords: Stroke, Imaging, Ventricular fibrillation, Heart Failure, Cardiac Magnetic Resonance Imaging, Editorials
DOI: https://doi.org/10.1161/circimaging.117.006908
Authors: Steffen E Petersen In X Stefan Neubauer In X
Abstract: No Abstract Available
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Hypertrabeculated Left Ventricular Myocardium in Relationship to Myocardial Function and Fibrosis: The Multi-Ethnic Study of Atherosclerosis.

Issue 3 Vol 284 Published on 2017-09-01 PMID 28418811 PMCID PMC5584648
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Keywords:
DOI: https://doi.org/10.1148/radiol.2017161995
Authors: Nadine Kawel-Boehm In X Robyn L McClelland In X Filip Zemrak In X Gabriella Captur In X W Gregory Hundley In X Chia-Ying Liu In X James C Moon In X Steffen E Petersen In X Bharath Ambale-Venkatesh In X João A C Lima In X David A Bluemke In X
Abstract: Purpose To determine if excess greater left ventricle (LV) trabeculation is associated with decreased average regional myocardial function, diffuse fibrosis, or both. Materials and Methods This was a HIPAA-compliant institutional board approved multicenter study, and all participants provided written informed consent. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent a comprehensive cardiac magnetic resonance (MR) examination. LV trabeculation was measured with the maximal apical fractal dimension (FD), which is a marker of endocardial complexity. Demographic covariates, cardiovascular risk factors, and cardiac MR measurements were compared across quartiles of FD. Associations between FD and peak regional systolic circumferential strain (Ecc) and T1 time, a surrogate for diffuse myocardial fibrosis, were assessed with multivariable linear regression models. Results A total of 1123 subjects (593 [52.8%] female; mean age, 67.1 years ± 8.7 [standard deviation]) underwent FD and Ecc measurement, and 992 (521 [52.5%] female; mean age, 67.1 years ± 8.7) underwent FD and T1 measurement. Mean FD was 1.2 ± 0.07 in both groups, and mean Ecc was -18.3 ± 2.27 in the subjects who underwent FD and Ecc measurement. Global volumes and ejection fraction showed no differences between FD quartiles. However, with increasing FD quartile, Ecc was greater (indicating worse average regional function) (P < .001). After adjustment, greater trabeculation was associated with 21% worse myocardial strain (relative to the mean) per unit change in FD (regression coefficient = 4.0%; P < .001). There was no association between the degree of trabeculation and diffuse fibrosis measured with T1 mapping. Conclusion Average regional LV function was worse in individuals with greater LV trabeculation, supporting the concept of hypertrabeculation being an epiphenomenon of disease. © RSNA, 2017.
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Pericardial, But Not Hepatic, Fat by CT Is Associated With CV Outcomes and Structure: The Multi-Ethnic Study of Atherosclerosis.

Issue 9 Vol 10 Published on 2017-09-01 PMID 28330662 PMCID PMC5591038
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Keywords: Obesity, Remodeling, Cardiac Magnetic Resonance Imaging, Pericardial Fat, Hepatic Fat
DOI: https://doi.org/10.1016/j.jcmg.2016.10.024
Authors: Ravi V Shah In X Amanda Anderson In X Jingzhong Ding In X Matthew Budoff In X Oliver Rider In X Steffen E Petersen In X Majken Karoline Jensen In X Manja Koch In X Matthew Allison In X Nadine Kawel-Boehm In X Jessica Wisocky In X Michael Jerosch-Herold In X Kenneth Mukamal In X João A C Lima In X Venkatesh L Murthy In X
Abstract:

Objectives

The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity.

Background

The impact of pericardial fat-a local fat depot encasing the heart-on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate.

Methods

We studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat). Poisson and Cox regression were used to estimate the annualized risk of incident hard atherosclerotic CVD (ASCVD), all-cause death, heart failure, all-cause CVD, hard coronary heart disease, and stroke as a function of pericardial and hepatic fat. Generalized additive models were used to assess the association between cardiac magnetic resonance indices of left ventricular (LV) structure and function and pericardial fat. Models were adjusted for relevant clinical, demographic, and cardiometabolic covariates.

Results

MESA study participants with higher pericardial and hepatic fat were more likely to be older, were more frequently men, and had a higher prevalence of cardiometabolic risk factors (including dysglycemia, dyslipidemia, hypertension), as well as adiposity-associated inflammation. Over a median 12.2-year follow-up (interquartile range: 11.6 to 12.8 years), pericardial fat was associated with a higher rate of incident hard ASCVD (standardized hazard ratio: 1.22; 95% confidence interval: 1.10 to 1.35; p = 0.0001). Hepatic fat by CT was not significantly associated with hard ASCVD (standardized hazard ratio: 0.96; 95% confidence interval: 0.86 to 1.08; p = 0.52). Higher pericardial fat was associated with greater indexed LV mass (37.8 g/m2.7 vs. 33.9 g/m2.7, highest quartile vs. lowest quartile; p < 0.01), LV mass-to-volume ratio (1.2 vs. 1.1, highest quartile vs. lowest quartile; p < 0.01). In adjusted models, a higher pericardial fat volume was associated with greater LV mass (p < 0.0001) and concentricity (p < 0.0001).

Conclusions

Pericardial fat is associated with poorer CVD prognosis and LV remodeling, independent of insulin resistance, inflammation, and CT measures of hepatic fat.
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Precision Functional Mapping of Individual Human Brains.

Issue 4 Vol 95 Published on 2017-08-01 PMID 28757305 PMCID PMC5576360
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Keywords: fMRI, Functional Connectivity, Brain Networks, Individual Variability, Myelin Mapping
DOI: https://doi.org/10.1016/j.neuron.2017.07.011
Authors: Evan M Gordon In X Timothy O Laumann In X Adrian W Gilmore In X Dillan J Newbold In X Deanna J Greene In X Jeffrey J Berg In X Mario Ortega In X Catherine Hoyt-Drazen In X Caterina Gratton In X Haoxin Sun In X Jacqueline M Hampton In X Rebecca S Coalson In X Annie L Nguyen In X Kathleen B McDermott In X Joshua S Shimony In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X Steven M Nelson In X Nico U F Dosenbach In X
Abstract: Human functional MRI (fMRI) research primarily focuses on analyzing data averaged across groups, which limits the detail, specificity, and clinical utility of fMRI resting-state functional connectivity (RSFC) and task-activation maps. To push our understanding of functional brain organization to the level of individual humans, we assembled a novel MRI dataset containing 5 hr of RSFC data, 6 hr of task fMRI, multiple structural MRIs, and neuropsychological tests from each of ten adults. Using these data, we generated ten high-fidelity, individual-specific functional connectomes. This individual-connectome approach revealed several new types of spatial and organizational variability in brain networks, including unique network features and topologies that corresponded with structural and task-derived brain features. We are releasing this highly sampled, individual-focused dataset as a resource for neuroscientists, and we propose precision individual connectomics as a model for future work examining the organization of healthy and diseased individual human brains.
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Key Questions Relating to Left Ventricular Noncompaction Cardiomyopathy: Is the Emperor Still Wearing Any Clothes?

Issue 6 Vol 33 Published on 2017-06-01 PMID 28395867 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.cjca.2017.01.017
Authors: Robert H Anderson In X Bjarke Jensen In X Timothy J Mohun In X Steffen E Petersen In X Nay Aung In X Filip Zemrak In X R Nils Planken In X David H MacIver In X
Abstract: The evidence is increasing that left ventricular noncompaction cardiomyopathy as it is currently defined does not represent a failure of compaction of pre-existing trabecular myocardium found during embryonic development to form the compact component of the ventricular walls. Neither is there evidence of which we are aware to favour the notion that the entity is a return to a phenotype seen in cold-blooded animals. It is also known that when seen in adults, the presence of excessive ventricular trabeculations does not portend a poor prognosis when the ejection fraction is normal, with the risks of complications such as arrhythmia and stroke being rare in this setting. It is also the case that images of "noncompaction" as provided from children or autopsy studies are quite different from the features observed clinically in asymptomatic adults with excessive trabeculation. Our review suggests that the presence of an excessively trabeculated left ventricular wall is not in itself a clinical entity. It is equally possible that the excessive trabeculation is no more than a bystander in the presence of additional lesions such as dilated cardiomyopathy, with the additional lesions being responsible for the reduced ejection fraction bringing a given patient to clinical attention. We, therefore, argue that the term "noncompaction cardiomyopathy" is misleading, because there is neither failure of compaction nor a cardiomyopathic process in most individuals that fulfill widely used diagnostic criteria.
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LV Noncompaction Cardiomyopathy or Just a Lot of Trabeculations?

Issue 6 Vol 10 Published on 2017-06-01 PMID 27568117 PMCID N/A
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Keywords: Cardiac Magnetic Resonance, Left Ventricular Noncompaction, Left Ventricular Trabeculations
DOI: https://doi.org/10.1016/j.jcmg.2016.03.014
Authors: Nay Aung In X Filip Zemrak In X Saidi A Mohiddin In X Steffen E Petersen In X
Abstract: No Abstract Available
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Coronary atherosclerotic plaque burden and composition by CT angiography in Caucasian and South Asian patients with stable chest pain.

Issue 5 Vol 18 Published on 2017-05-01 PMID 27225816 PMCID PMC5837200
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Keywords: Atherosclerosis, Coronary circulation, coronary artery disease, computed tomography, Ethnicity, Computed Tomography Angiography
DOI: https://doi.org/10.1093/ehjci/jew085
Authors: Peter R Villadsen In X Steffen E Petersen In X Damini Dey In X Lu Zou In X Shivali Patel In X Hafiz Naderi In X Katarzyna Gruszczynska In X Jan Baron In X L Ceri Davies In X Andrew Wragg In X Hans Erik Bøtker In X Francesca Pugliese In X
Abstract:

Aims

South Asian (SA) patients are known to have an increased incidence of acute cardiovascular events compared with Caucasians. The aim of this observational study was to compare the prevalence of coronary stenoses, the amount and composition of coronary atherosclerosis in a cohort of Caucasian and SA patients with stable chest pain, in non-acute settings.

Methods and results

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. In 963 consecutive Caucasian and SA patients undergoing coronary computed tomography angiography, atherosclerotic plaques were quantified using a semi-automated algorithm. The vessel per cent diameter and area stenosis were measured. Plaque composition was examined from the measurement of calcified, non-calcified, and total plaque burden. There were 420 Caucasian (238 males) and 543 SA (297 males) patients. Caucasian patients were older than SA patients (54.39 ± 11.65 vs. 49.83 ± 11.03 years) and had lower prevalence of diabetes (13.13 vs. 32.41%) and hyperlipidaemia (56.90 vs. 68.51%) (all P-values <0.001). After adjusting for differences in cardiovascular risk factors, there were no differences in per cent diameter and area stenosis, and no difference in the proportions of patients with one-, two-, or three-vessel disease. There was no difference in total plaque burden; however, the per cent non-calcified plaque composition was lower in Caucasians compared with SA (80.95 vs. 90.42%; P-value <0.001).

Conclusion

This study conducted in non-acute settings showed an ethnic difference in composition of coronary atherosclerotic plaque with lower non-calcified composition in Caucasian patients compared with SA patients, which was independent of age, diabetes, hyperlipidaemia, and the other available cardiovascular risk factors.
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Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

Issue 7 Vol 103 Published on 2017-04-01 PMID 28077465 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1136/heartjnl-2016-310529
Authors: Bart S Ferket In X M G Myriam Hunink In X Mohammed Khanji In X Isha Agarwal In X Kirsten E Fleischmann In X Steffen E Petersen In X
Abstract:

Objective

There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds.

Methods

We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%.

Results

Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50.

Conclusions

Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.
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Face processing in adolescents with positive and negative threat bias.

Issue 5 Vol 47 Published on 2017-04-01 PMID 27873557 PMCID PMC5500190
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Keywords: Visual cortex, Parietal lobe, Attention, fMRI, Anxiety, Orienting, Fusiform Gyrus
DOI: https://doi.org/10.1017/s003329171600310x
Authors: C M Sylvester In X S E Petersen In X J L Luby In X D M Barch In X
Abstract:

Background

Individuals with anxiety disorders exhibit a 'vigilance-avoidance' pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as 'threat bias'. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces.

Method

Subjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging.

Results

Adolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset.

Conclusions

Threat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.
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Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

Open Access Issue 3 Vol 27 Published on 2017-03-01 PMID 28062515 PMCID PMC5452276
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Keywords: Development, Network, fMRI, enrichment, Initiating Joint Attention
DOI: https://doi.org/10.1093/cercor/bhw403
Authors: Adam T Eggebrecht In X Jed T Elison In X Eric Feczko In X Alexandre Todorov In X Jason J Wolff In X Sridhar Kandala In X Chloe M Adams In X Abraham Z Snyder In X John D Lewis In X Annette M Estes In X Lonnie Zwaigenbaum In X Kelly N Botteron In X Robert C McKinstry In X John N Constantino In X Alan Evans In X Heather C Hazlett In X Stephen Dager In X Sarah J Paterson In X Robert T Schultz In X Martin A Styner In X Guido Gerig In X Samir Das In X Penelope Kostopoulos In X In X Bradley L Schlaggar In X Steven E Petersen In X Joseph Piven In X John R Pruett In X
Abstract: Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.
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Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks.

Issue 3 Vol 27 Published on 2017-03-01 PMID 27095824 PMCID PMC6411212
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Keywords: fMRI, decision-making, Networks, Executive Control
DOI: https://doi.org/10.1093/cercor/bhw092
Authors: C Gratton In X M Neta In X H Sun In X E J Ploran In X B L Schlaggar In X M E Wheeler In X S E Petersen In X S M Nelson In X
Abstract: Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions.
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Comprehensive analysis in 'Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks.' reveals critical findings. Exceptional work by Gratton:
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Preparatory Engagement of Cognitive Control Networks Increases Late in Childhood.

Issue 3 Vol 27 Published on 2017-03-01 PMID 26972753 PMCID PMC6317491
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Keywords: Development, fMRI, Adolescence, Task-switching, Fronto-parietal
DOI: https://doi.org/10.1093/cercor/bhw046
Authors: Jessica A Church In X Silvia A Bunge In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The ability to engage task control flexibly, especially in anticipation of task demands, is beneficial when juggling different tasks. We investigated whether children in late childhood or early adolescence engaged preparatory task control similar to adults in a trial-wise cued task-switching paradigm. Twenty-eight children (aged 9-15 years) and 30 adults (aged 21-30 years) participated in an fMRI study in which the Cue (preparatory) period across 2 tasks was analyzed separately from the execution of the tasks (the Target period). Children performed more slowly and less accurately than adults, and showed behavioral improvement within the child group age range of 9-15 years. Children exhibited weaker Cue period activation than adults within a number of putative cognitive control regions. In contrast, children exhibited greater activity than adults in several regions, including sensorimotor areas, during the Target period. Children who activated cognitive control-related regions more during the Cue period tended to activate the Target signal age-related regions less, and this correlated with improved accuracy and reaction time on the task, as well as age. The results endorse previous findings that preparatory cognitive control systems are still developing in late childhood, but add new evidence of age-related shifts in activity at the trial level.
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Excited to share our new paper, 'Preparatory Engagement of Cognitive Control Networks Increases Late in Childhood.', with Church et al. Always a pleasure to work with such a great team:
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Dorsal Anterior Cingulate, Medial Superior Frontal Cortex, and Anterior Insula Show Performance Reporting-Related Late Task Control Signals.

Issue 3 Vol 27 Published on 2017-03-01 PMID 26972752 PMCID PMC6059248
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Keywords: Error, Ambiguity, Functional Networks, Task Control, Performance Reporting
DOI: https://doi.org/10.1093/cercor/bhw053
Authors: Maital Neta In X Steven M Nelson In X Steven E Petersen In X
Abstract: The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control.
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Left Atrial Structure in Relationship to Age, Sex, Ethnicity, and Cardiovascular Risk Factors: MESA (Multi-Ethnic Study of Atherosclerosis).

Issue 2 Vol 10 Published on 2017-02-01 PMID 28196797 PMCID PMC5319802
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Keywords: Body surface area, Magnetic Resonance Imaging
DOI: https://doi.org/10.1161/circimaging.116.005379
Authors: Filip Zemrak In X Bharath Ambale-Venkatesh In X Gabriella Captur In X Jonathan Chrispin In X Ela Chamera In X Mohammadali Habibi In X Saman Nazarian In X Saidi A Mohiddin In X James C Moon In X Steffen E Petersen In X João A C Lima In X David A Bluemke In X
Abstract:

Background

Left atrial (LA) size is a marker of diastolic function and is associated with atrial fibrillation and cardiovascular outcomes. However, there are no large population studies measuring LA structure. The relationship of demographics and cardiovascular risk factors to LA size is largely unknown. This study aimed to determine associations of LA size with demographic factors, cardiac structure and function, and cardiovascular risk factors.

Methods and results

LA volume indexed to body surface area was measured by cardiovascular magnetic resonance steady-state free precession and fast gradient echo cine long- and short-axis images in 2576 asymptomatic participants of MESA ([Multi-Ethnic Study of Atherosclerosis] 68.7 years, 53.0% women, white 42.2%, Chinese American 12.0%, black 24.5%, and Hispanic 21.2%) using biplane and short-axis images. The mean LA volume index was 36.5±11.4 mL/m2 in the entire cohort and 35.5±10.1 mL/m2 in subjects free of cardiovascular risk factors (n=283). Multivariable analysis included adjustment for demographics, ethnicity, cardiovascular risk factors, serological studies, socioeconomic status, left ventricular structure, and medications. In the adjusted analysis, age (β=0.2 mL/m2 per year, P<0.0001), male sex (β=-4.2 mL/m2, P<0.0001), obesity (β=1.3 mL/m2, P<0.01), end-diastolic volume index (β=0.4 mL/m2, P<0.0001), Chinese American (β=-2.6 mL/m2, P<0.0001), and Hispanic (β=1.1 mL/m2, P<0.05) ethnicities were associated with LA volume index. Diabetes mellitus and smoking were not associated with LA volume index. LA volumes measured by steady-state free precession were 3% larger than by fast gradient echo cine cardiovascular magnetic resonance (P<0.001).

Conclusions

Age, sex, ethnicity and left ventricular structural parameters were associated with LA size. Importantly, the study provides reference values of normal LA volume index.
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Sharing our latest publication, 'Left Atrial Structure in Relationship to Age, Sex, Ethnicity, and Cardiovascular Risk Factors: MESA (Multi-Ethnic Study of Atherosclerosis).', with Zemrak et al. Proud of what we achieved together:
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Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort.

Open Access Issue 1 Vol 19 Published on 2017-02-01 PMID 28178995 PMCID PMC5304550
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Keywords: Reference values, Ventricular function, Cardiovascular Magnetic Resonance, Atrial Function
DOI: https://doi.org/10.1186/s12968-017-0327-9
Authors: Steffen E Petersen In X Nay Aung In X Mihir M Sanghvi In X Filip Zemrak In X Kenneth Fung In X Jose Miguel Paiva In X Jane M Francis In X Mohammed Y Khanji In X Elena Lukaschuk In X Aaron M Lee In X Valentina Carapella In X Young Jin Kim In X Paul Leeson In X Stefan K Piechnik In X Stefan Neubauer In X
Abstract:

Background

Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45-74.

Methods

Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45-54, 55-64, 65-74).

Results

After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females.

Conclusions

We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population.
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Our new article, 'Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort.', is finally out! Big thanks to Petersen and the coauthors for their dedication & insights:
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Brain Network Theory Can Predict Whether Neuropsychological Outcomes Will Differ from Clinical Expectations.

Issue 1 Vol 32 Published on 2017-02-01 PMID 27789443 PMCID N/A
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Keywords: Brain, Network, Cognition, Lesion, neuropsychology, Profile Agreement
DOI: https://doi.org/10.1093/arclin/acw091
Authors: David E Warren In X Natalie L Denburg In X Jonathan D Power In X Joel Bruss In X Eric J Waldron In X Haoxin Sun In X Steve E Petersen In X Daniel Tranel In X
Abstract:

Objective

Theories of brain-network organization based on neuroimaging data have burgeoned in recent years, but the predictive power of such theories for cognition and behavior has only rarely been examined. Here, predictions from clinical neuropsychologists about the cognitive profiles of patients with focal brain lesions were used to evaluate a brain-network theory (Warren et al., 2014).

Method

Neuropsychologists made predictions regarding the neuropsychological profiles of a neurological patient sample (N = 30) based on lesion location. The neuropsychologists then rated the congruence of their predictions with observed neuropsychological outcomes, in regard to the "severity" of neuropsychological deficits and the "focality" of neuropsychological deficits. Based on the network theory, two types of lesion locations were identified: "target" locations (putative hubs in a brain-wide network) and "control" locations (hypothesized to play limited roles in network function).

Results

We found that patients with lesions of target locations (N = 19) had deficits of greater than expected severity that were more widespread than expected, whereas patients with lesions of control locations (N = 11) showed milder, circumscribed deficits that were more congruent with expectations.

Conclusions

The findings for the target brain locations suggest that prevailing views of brain-behavior relationships may be sharpened and refined by integrating recently proposed network-oriented perspectives.
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Significant research milestone: 'Brain Network Theory Can Predict Whether Neuropsychological Outcomes Will Differ from Clinical Expectations.' published, demonstrating innovative approaches by Warren & team:
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Individual-specific features of brain systems identified with resting state functional correlations.

Issue N/A Vol 146 Published on 2017-02-01 PMID 27640749 PMCID PMC5321842
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Keywords: fMRI, Functional Connectivity, Individual Variability, Brain Systems
DOI: https://doi.org/10.1016/j.neuroimage.2016.08.032
Authors: Evan M Gordon In X Timothy O Laumann In X Babatunde Adeyemo In X Adrian W Gilmore In X Steven M Nelson In X Nico U F Dosenbach In X Steven E Petersen In X
Abstract: Recent work has made important advances in describing the large-scale systems-level organization of human cortex by analyzing functional magnetic resonance imaging (fMRI) data averaged across groups of subjects. However, new findings have emerged suggesting that individuals' cortical systems are topologically complex, containing small but reliable features that cannot be observed in group-averaged datasets, due in part to variability in the position of such features along the cortical sheet. This previous work has reported only specific examples of these individual-specific system features; to date, such features have not been comprehensively described. Here we used fMRI to identify cortical system features in individual subjects within three large cross-subject datasets and one highly sampled within-subject dataset. We observed system features that have not been previously characterized, but 1) were reliably detected across many scanning sessions within a single individual, and 2) could be matched across many individuals. In total, we identified forty-three system features that did not match group-average systems, but that replicated across three independent datasets. We described the size and spatial distribution of each non-group feature. We further observed that some individuals were missing specific system features, suggesting individual differences in the system membership of cortical regions. Finally, we found that individual-specific system features could be used to increase subject-to-subject similarity. Together, this work identifies individual-specific features of human brain systems, thus providing a catalog of previously unobserved brain system features and laying the foundation for detailed examinations of brain connectivity in individuals.
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Our study, 'Individual-specific features of brain systems identified with resting state functional correlations.', is now published! Big congratulations to Gordon and the team for making this happen:
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The impact of cardiovascular risk factors on cardiac structure and function: Insights from the UK Biobank imaging enhancement study.

Open Access Issue 10 Vol 12 Published on 2017-01-01 PMID 28973022 PMCID PMC5626035
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Keywords:
DOI: https://doi.org/10.1371/journal.pone.0185114
Authors: Steffen E Petersen In X Mihir M Sanghvi In X Nay Aung In X Jackie A Cooper In X José Miguel Paiva In X Filip Zemrak In X Kenneth Fung In X Elena Lukaschuk In X Aaron M Lee In X Valentina Carapella In X Young Jin Kim In X Stefan K Piechnik In X Stefan Neubauer In X
Abstract:

Aims

The UK Biobank is a large-scale population-based study utilising cardiovascular magnetic resonance (CMR) to generate measurements of atrial and ventricular structure and function. This study aimed to quantify the association between modifiable cardiovascular risk factors and cardiac morphology and function in individuals without known cardiovascular disease.

Methods

Age, sex, ethnicity (non-modifiable) and systolic blood pressure, diastolic blood pressure, smoking status, exercise, body mass index (BMI), high cholesterol, diabetes, alcohol intake (modifiable) were considered important cardiovascular risk factors. Multivariable regression models were built to ascertain the association of risk factors on left ventricular (LV), right ventricular (RV), left atrial (LA) and right atrial (RA) CMR parameters.

Results

4,651 participants were included in the analysis. All modifiable risk factors had significant effects on differing atrial and ventricular parameters. BMI was the modifiable risk factor most consistently associated with subclinical changes to CMR parameters, particularly in relation to higher LV mass (+8.3% per SD [4.3 kg/m2], 95% CI: 7.6 to 8.9%), LV (EDV: +4.8% per SD, 95% CI: 4.2 to 5.4%); ESV: +4.4% per SD, 95% CI: 3.5 to 5.3%), RV (EDV: +5.3% per SD, 95% CI: 4.7 to 5.9%; ESV: +5.4% per SD, 95% CI: 4.5 to 6.4%) and LA maximal (+8.6% per SD, 95% CI: 7.4 to 9.7%) volumes. Increases in SBP were associated with higher LV mass (+6.8% per SD, 95% CI: 5.9 to 7.7%), LV (EDV: +4.5% per SD, 95% CI: 3.6 to 5.4%; ESV: +2.0% per SD, 95% CI: 0.8 to 3.3%) volumes. The presence of diabetes or high cholesterol resulted in smaller volumes and lower ejection fractions.

Conclusions

Modifiable risk factors are associated with subclinical alterations in structure and function in all four cardiac chambers. BMI and systolic blood pressure are the most important modifiable risk factors affecting CMR parameters known to be linked to adverse outcomes.
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Breakthrough research 'The impact of cardiovascular risk factors on cardiac structure and function: Insights from the UK Biobank imaging enhancement study.' by Petersen & team reshapes scientific understanding:
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The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments.

Open Access Issue 1 Vol 19 Published on 2017-01-01 PMID 28187739 PMCID PMC5303267
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Keywords: Imaging, Patient Management, Registry, Cardiovascular Magnetic Resonance, Therapeutic Implications
DOI: https://doi.org/10.1186/s12968-016-0321-7
Authors: In X Raymond Y Kwong In X Steffen E Petersen In X Jeanette Schulz-Menger In X Andrew E Arai In X Scott E Bingham In X Yucheng Chen In X Yuna L Choi In X Ricardo C Cury In X Vanessa M Ferreira In X Scott D Flamm In X Kevin Steel In X W Patricia Bandettini In X Edward T Martin In X Leelakrishna Nallamshetty In X Stefan Neubauer In X Subha V Raman In X Erik B Schelbert In X Uma S Valeti In X Jie Jane Cao In X Nathaniel Reichek In X Alistair A Young In X Lyuba Fexon In X Misha Pivovarov In X Victor A Ferrari In X Orlando P Simonetti In X
Abstract:

Background

With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR.

Methods

The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR). The GCMR team has developed a web-based data infrastructure, data use policy and participation agreement, data-harmonizing methods, and site-training tools based on results from an international survey of CMR programs.

Results

At present, 17 CMR programs have established a legal agreement to participate in GCMR, amongst them 10 have contributed CMR data, totaling 62,456 studies. There is currently a predominance of CMR centers with more than 10 years of experience (65%), and the majority are located in the United States (63%). The most common clinical indications for CMR have included assessment of cardiomyopathy (21%), myocardial viability (16%), stress CMR perfusion for chest pain syndromes (16%), and evaluation of etiology of arrhythmias or planning of electrophysiological studies (15%) with assessment of cardiomyopathy representing the most rapidly growing indication in the past decade. Most CMR studies involved the use of gadolinium-based contrast media (95%).

Conclusions

We present the goals, mission and vision, infrastructure, preliminary results, and challenges of the GCMR.

Trial registration

Identification number on ClinicalTrials.gov: NCT02806193 . Registered 17 June 2016.
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Significant research milestone: 'The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments.' published, demonstrating innovative approaches by Unknown & team:
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Individual Variability of the System-Level Organization of the Human Brain.

Issue 1 Vol 27 Published on 2017-01-01 PMID 26464473 PMCID PMC5939195
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Keywords: fMRI, Functional Connectivity, Individual Variability, Brain Systems
DOI: https://doi.org/10.1093/cercor/bhv239
Authors: Evan M Gordon In X Timothy O Laumann In X Babatunde Adeyemo In X Steven E Petersen In X
Abstract: Recent functional magnetic resonance imaging-based resting-state functional connectivity analyses of group average data have characterized large-scale systems that represent a high level in the organizational hierarchy of the human brain. These systems are likely to vary spatially across individuals, even after anatomical alignment, but the characteristics of this variance are unknown. Here, we characterized large-scale brain systems across two independent datasets of young adults. In these individuals, we were able to identify brain systems that were similar to those described in the group average, and we observed that individuals had consistent topological arrangement of the system features present in the group average. However, the size of system features varied across individuals in systematic ways, such that expansion of one feature of a given system predicted expansion of other parts of the system. Individual-specific systems also contained unique topological features not present in group average systems; some of these features were consistent across a minority of individuals. These effects were observed even after controlling for data quality and for the accuracy of anatomical registration. The variability characterized here has important implications for cognitive neuroscience investigations, which often assume the functional equivalence of aligned brain regions across individuals.
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Breakthrough research 'Individual Variability of the System-Level Organization of the Human Brain.' by Gordon & team reshapes scientific understanding:
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Left Ventricular Noncompaction, or Is It?

Issue 20 Vol 68 Published on 2016-11-01 PMID 27855807 PMCID N/A
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Keywords: Prognosis, Cmr, Lvnc, Trabeculations
DOI: https://doi.org/10.1016/j.jacc.2016.09.912
Authors: Nay Aung In X Filip Zemrak In X Steffen E Petersen In X
Abstract: No Abstract Available
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Delighted to announce our latest publication 'Left Ventricular Noncompaction, or Is It?' by Aung et al:
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Cardiovascular Risk Assessment: A Systematic Review of Guidelines.

Issue 10 Vol 165 Published on 2016-11-01 PMID 27618509 PMCID N/A
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Keywords:
DOI: https://doi.org/10.7326/m16-1110
Authors: Mohammed Y Khanji In X Vinícius V S Bicalho In X Claudia N van Waardhuizen In X Bart S Ferket In X Steffen E Petersen In X M G Myriam Hunink In X
Abstract:

Background

Many guidelines exist for screening and risk assessment for the primary prevention of cardiovascular disease in apparently healthy persons.

Purpose

To systematically review current primary prevention guidelines on adult cardiovascular risk assessment and highlight the similarities and differences to aid clinician decision making.

Data sources

Publications in MEDLINE and CINAHL between 3 May 2009 and 30 June 2016 were identified. On 30 June 2016, the Guidelines International Network International Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and Web sites of organizations responsible for guideline development were searched.

Study selection

2 reviewers screened titles and abstracts to identify guidelines from Western countries containing recommendations for cardiovascular risk assessment for healthy adults.

Data extraction

2 reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines for Research and Evaluation II instrument, and 1 extracted the recommendations.

Data synthesis

Of the 21 guidelines, 17 showed considerable rigor of development. These recommendations address assessment of total cardiovascular risk (5 guidelines), dysglycemia (7 guidelines), dyslipidemia (2 guidelines), and hypertension (3 guidelines). All but 1 recommendation advocates for screening, and most include prediction models integrating several relatively simple risk factors for either deciding on further screening or guiding subsequent management. No consensus on the strategy for screening, recommended target population, screening tests, or treatment thresholds exists.

Limitation

Only guidelines developed by Western national or international medical organizations were included.

Conclusion

Considerable discrepancies in cardiovascular screening guidelines still exist, with no consensus on optimum screening strategies or treatment threshold.

Primary funding source

Barts Charity.
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Delighted to announce our latest publication 'Cardiovascular Risk Assessment: A Systematic Review of Guidelines.' by Khanji et al:
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Evaluation of Denoising Strategies to Address Motion-Correlated Artifacts in Resting-State Functional Magnetic Resonance Imaging Data from the Human Connectome Project.

Issue 9 Vol 6 Published on 2016-11-01 PMID 27571276 PMCID PMC5105353
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Keywords: fMRI, Motion, Resting state, Denoising, Functional Connectivity, Artifact, independent component analysis, Human Connectome Project
DOI: https://doi.org/10.1089/brain.2016.0435
Authors: Gregory C Burgess In X Sridhar Kandala In X Dan Nolan In X Timothy O Laumann In X Jonathan D Power In X Babatunde Adeyemo In X Michael P Harms In X Steven E Petersen In X Deanna M Barch In X
Abstract: Like all resting-state functional connectivity data, the data from the Human Connectome Project (HCP) are adversely affected by structured noise artifacts arising from head motion and physiological processes. Functional connectivity estimates (Pearson's correlation coefficients) were inflated for high-motion time points and for high-motion participants. This inflation occurred across the brain, suggesting the presence of globally distributed artifacts. The degree of inflation was further increased for connections between nearby regions compared with distant regions, suggesting the presence of distance-dependent spatially specific artifacts. We evaluated several denoising methods: censoring high-motion time points, motion regression, the FMRIB independent component analysis-based X-noiseifier (FIX), and mean grayordinate time series regression (MGTR; as a proxy for global signal regression). The results suggest that FIX denoising reduced both types of artifacts, but left substantial global artifacts behind. MGTR significantly reduced global artifacts, but left substantial spatially specific artifacts behind. Censoring high-motion time points resulted in a small reduction of distance-dependent and global artifacts, eliminating neither type. All denoising strategies left differences between high- and low-motion participants, but only MGTR substantially reduced those differences. Ultimately, functional connectivity estimates from HCP data showed spatially specific and globally distributed artifacts, and the most effective approach to address both types of motion-correlated artifacts was a combination of FIX and MGTR.
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So excited to see our paper, 'Evaluation of Denoising Strategies to Address Motion-Correlated Artifacts in Resting-State Functional Magnetic Resonance Imaging Data from the Human Connectome Project.', in print! A great team effort with Burgess et al.:
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Comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic review.

Issue 4 Vol 2 Published on 2016-10-01 PMID 29474724 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjqcco/qcw029
Authors: Claudia N van Waardhuizen In X Mohammed Y Khanji In X Tessa S S Genders In X Bart S Ferket In X Kirsten E Fleischmann In X M G Myriam Hunink In X Steffen E Petersen In X
Abstract: Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality globally. The most cost-effective imaging strategy to diagnose CAD in patients with stable chest pain is however uncertain. To review the evidence on comparative cost-effectiveness of different imaging strategies for patients presenting with stable chest pain symptoms suggestive for CAD. Systematic review. Studies performing a formal economic evaluation or decision analysis in the English language published between January 1995 and December 2015 were identified using PubMed, Medline (OvidSP), Embase, Web of Science, Cochrane economic evaluations library, and EconLit. Reviews and meta-analyses were excluded. Two independent reviewers assessed titles and abstracts. Of the 4498 titles identified, 70 met our selection criteria. One reviewer used a modified version of the CHEERS checklist to assess study quality. One reviewer extracted data on study details, which were checked by a second reviewer. There is a major heterogeneity between the available cost-effectiveness studies included in this study. The included studies compared very different testing strategies in very different ways and provided mostly short-term results. Strategies of no-testing and xECG were underrepresented. Nonetheless, the findings from this systematic review suggest that for patients with a low to intermediate prior probability of having obstructive CAD, computed tomography coronary angiography (CTCA) may be cost-effective as an initial diagnostic imaging test in comparison with CAG or other non-invasive diagnostic tests. If functional testing is required, stress echocardiography (SE) or single-photon emission computed tomography (SPECT) are suggested to be cost-effective initial strategies in patients with intermediate prior probability of CAD. Yet, other functional testing strategies such as xECG and positron-emission tomography (PET) scanning have not been studied as intensely. Immediate CAG is suggested to be a cost-effective strategy for patients at a high prior probability of having obstructive CAD whom may benefit from revascularization. The study emphasizes the inextricable link between clinical effectiveness and economic efficiency. Evidence suggests that the optimal diagnostic imaging strategy for individuals suspected of having CAD is CTCA for low and intermediate disease probability, followed by SE or SPECT as necessary, and invasive CAG for high disease probability. Further studies are needed to evaluate the cost-effectiveness of alternative non-invasive tests, including a no-testing strategy.
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Our new publication 'Comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic review.' provides groundbreaking perspectives by van Waardhuizen and team:
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Evidence for Two Independent Factors that Modify Brain Networks to Meet Task Goals.

Issue 5 Vol 17 Published on 2016-10-01 PMID 27783943 PMCID PMC5123792
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Keywords: fMRI, Graph theory, Brain Networks, Task Control
DOI: https://doi.org/10.1016/j.celrep.2016.10.002
Authors: Caterina Gratton In X Timothy O Laumann In X Evan M Gordon In X Babatunde Adeyemo In X Steven E Petersen In X
Abstract: Humans easily and flexibly complete a wide variety of tasks. To accomplish this feat, the brain appears to subtly adjust stable brain networks. Here, we investigate what regional factors underlie these modifications, asking whether networks are either altered at (1) regions activated by a given task or (2) hubs that interconnect different networks. We used fMRI "functional connectivity" (FC) to compare networks during rest and three distinct tasks requiring semantic judgments, mental rotation, and visual coherence. We found that network modifications during these tasks were independently associated with both regional activation and network hubs. Furthermore, active and hub regions were associated with distinct patterns of network modification (differing in their localization, topography of FC changes, and variability across tasks), with activated hubs exhibiting patterns consistent with task control. These findings indicate that task goals modify brain networks through two separate processes linked to local brain function and network hubs.
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Excited to share our new paper, 'Evidence for Two Independent Factors that Modify Brain Networks to Meet Task Goals.', with Gratton et al. Always a pleasure to work with such a great team:
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Cardiac Remodeling: Novel Insights From MESA.

Issue 10 Vol 9 Published on 2016-10-01 PMID 27639761 PMCID N/A
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Keywords: Aging, Longitudinal study, Torsion, risk factors, Left Ventricular
DOI: https://doi.org/10.1016/j.jcmg.2016.04.006
Authors: Steffen E Petersen In X
Abstract: No Abstract Available
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Our new publication 'Cardiac Remodeling: Novel Insights From MESA.' provides groundbreaking perspectives by Petersen and team:
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EACVI appropriateness criteria for the use of cardiovascular imaging in heart failure derived from European National Imaging Societies voting.

Issue 7 Vol 17 Published on 2016-07-01 PMID 27129538 PMCID N/A
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Keywords: Echocardiography, Heart Failure, Cardiac Computed Tomography, Nuclear Imaging, Appropriateness Criteria, Cardiovascular Imaging, Cardiac Resonance Imaging
DOI: https://doi.org/10.1093/ehjci/jew081
Authors: Madalina Garbi In X Thor Edvardsen In X Jeroen Bax In X Steffen E Petersen In X Theresa McDonagh In X Gerasimos Filippatos In X Patrizio Lancellotti In X In X
Abstract: This paper presents the first European appropriateness criteria for the use of cardiovascular imaging in heart failure, derived from voting of the European National Imaging Societies representatives. The paper describes the development process and discusses the results.
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Multivariate pattern classification of pediatric Tourette syndrome using functional connectivity MRI.

Open Access Issue 4 Vol 19 Published on 2016-07-01 PMID 26834084 PMCID PMC4945470
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DOI: https://doi.org/10.1111/desc.12407
Authors: Deanna J Greene In X Jessica A Church In X Nico U F Dosenbach In X Ashley N Nielsen In X Babatunde Adeyemo In X Binyam Nardos In X Steven E Petersen In X Kevin J Black In X Bradley L Schlaggar In X
Abstract: Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics. Individuals with TS would benefit greatly from advances in prediction of symptom timecourse and treatment effectiveness. As a first step, we applied a multivariate method - support vector machine (SVM) classification - to test whether patterns in brain network activity, measured with resting state functional connectivity (RSFC) MRI, could predict diagnostic group membership for individuals. RSFC data from 42 children with TS (8-15 yrs) and 42 unaffected controls (age, IQ, in-scanner movement matched) were included. While univariate tests identified no significant group differences, SVM classified group membership with ~70% accuracy (p < .001). We also report a novel adaptation of SVM binary classification that, in addition to an overall accuracy rate for the SVM, provides a confidence measure for the accurate classification of each individual. Our results support the contention that multivariate methods can better capture the complexity of some brain disorders, and hold promise for predicting prognosis and treatment outcome for individuals with TS.
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Salvage radiation therapy following radical prostatectomy. A national Danish study.

Issue 5 Vol 55 Published on 2016-05-01 PMID 26399602 PMCID N/A
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DOI: https://doi.org/10.3109/0284186x.2015.1088170
Authors: Maria Ervandian In X Morten Høyer In X Stine Elleberg Petersen In X Lisa Sengeløv In X Steinbjørn Hansen In X Mats Holmberg In X Joen Sveistrup In X Peter Meidahl Petersen In X Michael Borre In X
Abstract:

Background

The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort.

Material and methods

Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related characteristics were retrospectively retrieved from patient charts. The primary end point was biochemical progression-free survival (b-PFS).

Results

At the end of follow-up, 51% of the patients displayed a prostate-specific antigen (PSA) level <0.1 ng/ml. The three-year b-PFS rate for the total cohort was 57.0%. Nearly half of the patients (44%) received androgen deprivation therapy (ADT) in combination with SRT. Positive surgical tumour margins (p = 0.025) and ADT (p = 0.001) were the only markers independently correlated with b-PFS. In patients who received SRT without ADT, both a pre-SRT PSA level ≤0.5 ng/ml (p = 0.003) and pathological tumour stage T1-T2 (p = 0.036) independently correlated with b-PFS. Moreover, a duration between radical prostatectomy (RP) and SRT ≤29 months (p = 0.035) independently correlated with b-PFS in patients treated with ADT in combination with RT.

Conclusions

In patients treated for biochemical failure after RP, positive surgical tumour margins and PSA levels ≤0.5 ng/mL at the time of SRT were associated with a favourable outcome. Despite less favourable tumour characteristics, patients receiving SRT and ADT demonstrated improved b-PFS, and in particular, patients with PSA levels >0.2 ng/ml benefitted from additional ADT.
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Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

Issue 1 Vol 119 Published on 2016-04-01 PMID 26879287 PMCID PMC5512537
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Keywords: Toxicity, Bladder, Radiotherapy, prostate cancer, Patient-reported Outcome, Dose–response
DOI: https://doi.org/10.1016/j.radonc.2016.01.013
Authors: Maria Thor In X Caroline Olsson In X Jung Hun Oh In X Stine Elleberg Petersen In X David Alsadius In X Lise Bentzen In X Niclas Pettersson In X Ludvig Paul Muren In X Morten Høyer In X Gunnar Steineck In X Joseph O Deasy In X
Abstract:

Background and purpose

Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose.

Materials and methods

Data were taken from two Scandinavian studies (N=207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to-follow-up: 3.6-6.4y). Within and across cohorts, bladder dose-volume parameters were tested as predictors for GU symptom domains identified from two study-specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (Az).

Results

For the identified Incontinence (2-5 symptoms), Obstruction (3-5 symptoms), and Urgency (2-7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (Az: 0.53-0.57) and Urgency (Az: 0.60). For Obstruction, performance increased for the across cohort analysis (Az: 0.61-0.64).

Conclusions

Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses.
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A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging.

Open Access Issue 2 Vol 29 Published on 2016-04-01 PMID 26811173 PMCID PMC4830888
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Keywords: MRI, Clinical Assessment, Cardiac Segmentation
DOI: https://doi.org/10.1007/s10334-015-0521-4
Authors: Peng Peng In X Karim Lekadir In X Ali Gooya In X Ling Shao In X Steffen E Petersen In X Alejandro F Frangi In X
Abstract: Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice.
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Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

Issue 7 Vol 193 Published on 2016-04-01 PMID 26550687 PMCID PMC5440091
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Keywords: Cardiac function, chronic obstructive pulmonary disease, Cardiac Magnetic Resonance, Lung Hyperinflation, Fluticasone Furoate/vilanterol
DOI: https://doi.org/10.1164/rccm.201508-1647oc
Authors: Ian S Stone In X Neil C Barnes In X Wai-Yee James In X Dawn Midwinter In X Redha Boubertakh In X Richard Follows In X Leonette John In X Steffen E Petersen In X
Abstract:

Rationale

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations.

Objectives

To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance.

Methods

Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo.

Measurements and main results

There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo.

Conclusions

Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).
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Unmasking Language Lateralization in Human Brain Intrinsic Activity.

Issue 4 Vol 26 Published on 2016-04-01 PMID 25636911 PMCID PMC4785953
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Keywords: Resting-state, Hemispheric Asymmetry, Attention Network, Global Signal, Semantic Network
DOI: https://doi.org/10.1093/cercor/bhv007
Authors: Mark McAvoy In X Anish Mitra In X Rebecca S Coalson In X Giovanni d'Avossa In X James L Keidel In X Steven E Petersen In X Marcus E Raichle In X
Abstract: Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal.
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UK Biobank's cardiovascular magnetic resonance protocol.

Open Access Issue N/A Vol 18 Published on 2016-02-01 PMID 26830817 PMCID PMC4736703
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DOI: https://doi.org/10.1186/s12968-016-0227-4
Authors: Steffen E Petersen In X Paul M Matthews In X Jane M Francis In X Matthew D Robson In X Filip Zemrak In X Redha Boubertakh In X Alistair A Young In X Sarah Hudson In X Peter Weale In X Steve Garratt In X Rory Collins In X Stefan Piechnik In X Stefan Neubauer In X
Abstract:

Background

UK Biobank's ambitious aim is to perform cardiovascular magnetic resonance (CMR) in 100,000 people previously recruited into this prospective cohort study of half a million 40-69 year-olds.

Methods/design

We describe the CMR protocol applied in UK Biobank's pilot phase, which will be extended into the main phase with three centres using the same equipment and protocols. The CMR protocol includes white blood CMR (sagittal anatomy, coronary and transverse anatomy), cine CMR (long axis cines, short axis cines of the ventricles, coronal LVOT cine), strain CMR (tagging), flow CMR (aortic valve flow) and parametric CMR (native T1 map).

Discussion

This report will serve as a reference to researchers intending to use the UK Biobank resource or to replicate the UK Biobank cardiovascular magnetic resonance protocol in different settings.
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Comparison of Cartesian and Non-Cartesian Real-Time MRI Sequences at 1.5T to Assess Velar Motion and Velopharyngeal Closure during Speech.

Open Access Issue 4 Vol 11 Published on 2016-01-01 PMID 27073905 PMCID PMC4830548
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DOI: https://doi.org/10.1371/journal.pone.0153322
Authors: Andreia C Freitas In X Marzena Wylezinska In X Malcolm J Birch In X Steffen E Petersen In X Marc E Miquel In X
Abstract: Dynamic imaging of the vocal tract using real-time MRI has been an active and growing area of research, having demonstrated great potential to become routinely performed in the clinical evaluation of speech and swallowing disorders. Although many technical advances have been made in regards to acquisition and reconstruction methodologies, there is still no consensus in best practice protocols. This study aims to compare Cartesian and non-Cartesian real-time MRI sequences, regarding image quality and temporal resolution trade-off, for dynamic speech imaging. Five subjects were imaged at 1.5T, while performing normal phonation, in order to assess velar motion and velopharyngeal closure. Data was acquired using both Cartesian and non-Cartesian (spiral and radial) real-time sequences at five different spatial-temporal resolution sets, between 10 fps (1.7×1.7×10 mm3) and 25 fps (1.5×1.5×10 mm3). Only standard scanning resources provided by the MRI scanner manufacturer were used to ensure easy applicability to clinical evaluation and reproducibility. Data sets were evaluated by comparing measurements of the velar structure, dynamic contrast-to-noise ratio and image quality visual scoring. Results showed that for all proposed sequences, FLASH spiral acquisitions provided higher contrast-to-noise ratio, up to a 170.34% increase at 20 fps, than equivalent bSSFP Cartesian acquisitions for the same spatial-temporal resolution. At higher frame rates (22 and 25 fps), spiral protocols were optimal and provided higher CNR and visual scoring than equivalent radial protocols. Comparison of dynamic imaging at 10 and 22 fps for radial and spiral acquisitions revealed no significant difference in CNR performance, thus indicating that temporal resolution can be doubled without compromising spatial resolution (1.9×1.9 mm2) or CNR. In summary, this study suggests that the use of FLASH spiral protocols should be preferred over bSSFP Cartesian for the dynamic imaging of velopharyngeal closure, as it allows for an improvement in CNR and overall image quality without compromising spatial-temporal resolution.
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Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary?

Open Access Issue N/A Vol 18 Published on 2016-01-01 PMID 26803468 PMCID PMC4724400
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DOI: https://doi.org/10.1186/s12968-016-0226-5
Authors: Stephen Hamshere In X Daniel A Jones In X Cyril Pellaton In X Danielle Longchamp In X Tom Burchell In X Saidi Mohiddin In X James C Moon In X Jens Kastrup In X Didier Locca In X Steffen E Petersen In X Mark Westwood In X Anthony Mathur In X
Abstract:

Background

AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR).

Methods

CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers.

Results

85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 ± 3.21%, 95% limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs. (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001.

Conclusions

AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians.
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Cost-minimization analysis of three decision strategies for cardiac revascularization: results of the "suspected CAD" cohort of the european cardiovascular magnetic resonance registry.

Open Access Issue N/A Vol 18 Published on 2016-01-01 PMID 26754743 PMCID PMC4709988
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Keywords:
DOI: https://doi.org/10.1186/s12968-015-0222-1
Authors: Karine Moschetti In X Steffen E Petersen In X Guenter Pilz In X Raymond Y Kwong In X Jean-Blaise Wasserfallen In X Massimo Lombardi In X Grigorios Korosoglou In X Albert C Van Rossum In X Oliver Bruder In X Heiko Mahrholdt In X Juerg Schwitter In X
Abstract:

Background

Coronary artery disease (CAD) continues to be one of the top public health burden. Perfusion cardiovascular magnetic resonance (CMR) is generally accepted to detect CAD, while data on its cost effectiveness are scarce. Therefore, the goal of the study was to compare the costs of a CMR-guided strategy vs two invasive strategies in a large CMR registry.

Methods

In 3'647 patients with suspected CAD of the EuroCMR-registry (59 centers/18 countries) costs were calculated for diagnostic examinations (CMR, X-ray coronary angiography (CXA) with/without FFR), revascularizations, and complications during a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive CXA and revascularization at the discretion of the treating physician (=CMR + CXA-strategy). In the hypothetical invasive arm, costs were calculated for an initial CXA and a FFR in vessels with ≥50% stenoses (=CXA + FFR-strategy) and the same proportion of revascularizations and complications were applied as in the CMR + CXA-strategy. In the CXA-only strategy, costs included those for CXA and for revascularizations of all ≥50% stenoses. To calculate the proportion of patients with ≥50% stenoses, the stenosis-FFR relationship from the literature was used. Costs of the three strategies were determined based on a third payer perspective in 4 healthcare systems.

Results

Revascularizations were performed in 6.2%, 4.5%, and 12.9% of all patients, patients with atypical chest pain (n = 1'786), and typical angina (n = 582), respectively; whereas complications (=all-cause death and non-fatal infarction) occurred in 1.3%, 1.1%, and 1.5%, respectively. The CMR + CXA-strategy reduced costs by 14%, 34%, 27%, and 24% in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59%, 52%, 61% and 71%, respectively, versus the CXA-only strategy. In patients with typical angina, cost savings by CMR + CXA vs CXA + FFR were minimal in the German (2.3%), intermediate in the US and Swiss (11.6% and 12.8%, respectively), and remained substantial in the UK (18.9%) systems. Sensitivity analyses proved the robustness of results.

Conclusions

A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. However, in the subgroup of patients with typical angina, cost savings were only minimal to moderate.
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Generation and Evaluation of a Cortical Area Parcellation from Resting-State Correlations.

Issue 1 Vol 26 Published on 2016-01-01 PMID 25316338 PMCID PMC4677978
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Keywords: Resting state, Functional Connectivity, Cortical Areas, Parcellation
DOI: https://doi.org/10.1093/cercor/bhu239
Authors: Evan M Gordon In X Timothy O Laumann In X Babatunde Adeyemo In X Jeremy F Huckins In X William M Kelley In X Steven E Petersen In X
Abstract: The cortical surface is organized into a large number of cortical areas; however, these areas have not been comprehensively mapped in the human. Abrupt transitions in resting-state functional connectivity (RSFC) patterns can noninvasively identify locations of putative borders between cortical areas (RSFC-boundary mapping; Cohen et al. 2008). Here we describe a technique for using RSFC-boundary maps to define parcels that represent putative cortical areas. These parcels had highly homogenous RSFC patterns, indicating that they contained one unique RSFC signal; furthermore, the parcels were much more homogenous than a null model matched for parcel size when tested in two separate datasets. Several alternative parcellation schemes were tested this way, and no other parcellation was as homogenous as or had as large a difference compared with its null model. The boundary map-derived parcellation contained parcels that overlapped with architectonic mapping of areas 17, 2, 3, and 4. These parcels had a network structure similar to the known network structure of the brain, and their connectivity patterns were reliable across individual subjects. These observations suggest that RSFC-boundary map-derived parcels provide information about the location and extent of human cortical areas. A parcellation generated using this method is available at http://www.nil.wustl.edu/labs/petersen/Resources.html.
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Tasks Driven by Perceptual Information Do Not Recruit Sustained BOLD Activity in Cingulo-Opercular Regions.

Issue 1 Vol 26 Published on 2016-01-01 PMID 25150283 PMCID PMC4677973
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Keywords: fMRI, Cognitive Control, Task Set, Sustained Bold, Task-control Signals
DOI: https://doi.org/10.1093/cercor/bhu187
Authors: Joseph W Dubis In X Joshua S Siegel In X Maital Neta In X Kristina M Visscher In X Steven E Petersen In X
Abstract: Sustained blood oxygen level dependent (BOLD) signal in the dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) is found in a broad majority of tasks examined and is believed to function as a putative task set maintenance signal. For example, a meta-analysis investigating task-control signals identified the dorsal anterior cingulate cortex and anterior insula as exhibiting sustained activity across a variety of task types. Re-analysis of tasks included in that meta-analysis showed exceptions, suggesting that tasks where the information necessary to determine a response was present in the stimulus (i.e., perceptually driven) does not show strong sustained cingulo-opercular activity. In a new experiment, we tested the generality of this observation while addressing alternative explanations about sustained cingulo-opercular activity (including task difficulty and verbal vs. non-verbal task demands). A new, difficult, perceptually driven task was compared with 2 new tasks that depended on information beyond that provided by the stimulus. The perceptually driven task showed a lack of cingulo-opercular activity in contrast to the 2 newly constructed tasks. This finding supports the idea that sustained cingulo-opercular activity contributes to maintenance of task set in only a subset of tasks.
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Long-term neural and physiological phenotyping of a single human.

Open Access Issue N/A Vol 6 Published on 2015-12-01 PMID 26648521 PMCID PMC4682164
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Keywords:
DOI: https://doi.org/10.1038/ncomms9885
Authors: Russell A Poldrack In X Timothy O Laumann In X Oluwasanmi Koyejo In X Brenda Gregory In X Ashleigh Hover In X Mei-Yen Chen In X Krzysztof J Gorgolewski In X Jeffrey Luci In X Sung Jun Joo In X Ryan L Boyd In X Scott Hunicke-Smith In X Zack Booth Simpson In X Thomas Caven In X Vanessa Sochat In X James M Shine In X Evan Gordon In X Abraham Z Snyder In X Babatunde Adeyemo In X Steven E Petersen In X David C Glahn In X D Reese Mckay In X Joanne E Curran In X Harald H H Göring In X Melanie A Carless In X John Blangero In X Robert Dougherty In X Alexander Leemans In X Daniel A Handwerker In X Laurie Frick In X Edward M Marcotte In X Jeanette A Mumford In X
Abstract: Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders.
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Fractal Analysis of Myocardial Trabeculations in 2547 Study Participants: Multi-Ethnic Study of Atherosclerosis.

Issue 3 Vol 277 Published on 2015-12-01 PMID 26069924 PMCID PMC4666098
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Keywords:
DOI: https://doi.org/10.1148/radiol.2015142948
Authors: Gabriella Captur In X Filip Zemrak In X Vivek Muthurangu In X Steffen E Petersen In X Chunming Li In X Paul Bassett In X Nadine Kawel-Boehm In X William J McKenna In X Perry M Elliott In X João A C Lima In X David A Bluemke In X James C Moon In X
Abstract:

Purpose

To quantitatively determine the population variation and relationship of left ventricular (LV) trabeculation to LV function, structure, and clinical variables.

Materials and methods

This HIPAA-compliant multicenter study was approved by institutional review boards of participating centers. All participants provided written informed consent. Participants from the Multi-Ethnic Study of Atherosclerosis with cardiac magnetic resonance (MR) data were evaluated to quantify LV trabeculation as a fractal dimension (FD). Entire cohort participants free of cardiac disease, hypertrophy, hypertension, and diabetes were stratified by body mass index (BMI) into three reference groups (BMI <25 kg/m(2); BMI ≥25 kg/m(2) to <30 kg/m(2); and BMI ≥30 kg/m(2)) to explore maximal apical FD (FDMaxApical). Multivariable linear regression models determined the relationship between FD and other parameters.

Results

Included were 2547 participants (mean age, 68.7 years ± 9.1 [standard deviation]; 1211 men). FDMaxApical are in arbitrary units. FDMaxApical reference ranges for BMI 30 kg/m(2) or greater (n = 163), 25 kg/m(2) or greater to less than 30 kg/m(2) (n = 206), and less than 25 kg/m(2) (n = 235) were 1.203 ± 0.06 (95% confidence interval: 1.194, 1.212), 1.194 ± 0.06 (95% confidence interval: 1.186, 1.202), and 1.169 ± 0.05 (95% confidence interval: 1.162, 1.176), respectively. In the entire cohort, adjusted for anthropometrics, trabeculation was higher in African American participants (standardized β [sβ] = 0.09; P ≤ .001) and Hispanic participants (sβ = 0.05; P = .013) compared with white participants and was also higher in African American participants compared with Chinese American participants (sβ = 0.08; P = .01), and this persisted after adjustment for hypertension and LV size. Hypertension (sβ = 0.07; P < .001), LV mass (sβ = 0.22; P < .001), and wall thickness (sβ = 0.27; P < .001) were positively associated with FDMaxApical even after adjustment. In the group with BMIs less than 25 kg/m(2), Chinese American participants had less trabeculation than white participants (sβ = -0.15; P = .032).

Conclusion

Fractal analysis of cardiac MR imaging data measures endocardial complexity, which helps to differentiate normal from abnormal trabecular patterns in healthy versus diseased hearts. Trabeculation is influenced by race and/or ethnicity and, more importantly, by cardiac loading conditions and comorbidities. Clinicians who interpret cine MR imaging data should expect slightly less endocardial complexity in Chinese American patients and more in African American patients, Hispanic patients, hypertensive patients, and those with hypertrophy.
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Brain Networks and Cognitive Architectures.

Issue 1 Vol 88 Published on 2015-10-01 PMID 26447582 PMCID PMC4598639
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Keywords:
DOI: https://doi.org/10.1016/j.neuron.2015.09.027
Authors: Steven E Petersen In X Olaf Sporns In X
Abstract: Most accounts of human cognitive architectures have focused on computational accounts of cognition while making little contact with the study of anatomical structures and physiological processes. A renewed convergence between neurobiology and cognition is well under way. A promising area arises from the overlap between systems/cognitive neuroscience on the one side and the discipline of network science on the other. Neuroscience increasingly adopts network tools and concepts to describe the operation of collections of brain regions. Beyond just providing illustrative metaphors, network science offers a theoretical framework for approaching brain structure and function as a multi-scale system composed of networks of neurons, circuits, nuclei, cortical areas, and systems of areas. This paper views large-scale networks at the level of areas and systems, mostly on the basis of data from human neuroimaging, and how this view of network structure and function has begun to illuminate our understanding of the biological basis of cognitive architectures.
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Fractal frontiers in cardiovascular magnetic resonance: towards clinical implementation.

Open Access Issue N/A Vol 17 Published on 2015-09-01 PMID 26346700 PMCID PMC4562373
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DOI: https://doi.org/10.1186/s12968-015-0179-0
Authors: Gabriella Captur In X Audrey L Karperien In X Chunming Li In X Filip Zemrak In X Catalina Tobon-Gomez In X Xuexin Gao In X David A Bluemke In X Perry M Elliott In X Steffen E Petersen In X James C Moon In X
Abstract: Many of the structures and parameters that are detected, measured and reported in cardiovascular magnetic resonance (CMR) have at least some properties that are fractal, meaning complex and self-similar at different scales. To date however, there has been little use of fractal geometry in CMR; by comparison, many more applications of fractal analysis have been published in MR imaging of the brain.This review explains the fundamental principles of fractal geometry, places the fractal dimension into a meaningful context within the realms of Euclidean and topological space, and defines its role in digital image processing. It summarises the basic mathematics, highlights strengths and potential limitations of its application to biomedical imaging, shows key current examples and suggests a simple route for its successful clinical implementation by the CMR community.By simplifying some of the more abstract concepts of deterministic fractals, this review invites CMR scientists (clinicians, technologists, physicists) to experiment with fractal analysis as a means of developing the next generation of intelligent quantitative cardiac imaging tools.
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Splenic Switch-off: A Tool to Assess Stress Adequacy in Adenosine Perfusion Cardiac MR Imaging.

Issue 3 Vol 276 Published on 2015-09-01 PMID 25923223 PMCID N/A
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DOI: https://doi.org/10.1148/radiol.2015142059
Authors: Charlotte Manisty In X David P Ripley In X Anna S Herrey In X Gabriella Captur In X Timothy C Wong In X Steffen E Petersen In X Sven Plein In X Charles Peebles In X Erik B Schelbert In X John P Greenwood In X James C Moon In X
Abstract:

Purpose

To investigate the pharmacology and potential clinical utility of splenic switch-off to identify understress in adenosine perfusion cardiac magnetic resonance (MR) imaging.

Materials and methods

Splenic switch-off was assessed in perfusion cardiac MR examinations from 100 patients (mean age, 62 years [age range, 18-87 years]) by using three stress agents (adenosine, dobutamine, and regadenoson) in three different institutions, with appropriate ethical permissions. In addition, 100 negative adenosine images from the Clinical Evaluation of MR Imaging in Coronary Heart Disease (CE-MARC) trial (35 false and 65 true negative; mean age, 59 years [age range, 40-73 years]) were assessed to ascertain the clinical utility of the sign to detect likely pharmacologic understress. Differences in splenic perfusion were compared by using Wilcoxon signed rank or Wilcoxon rank sum tests, and true-negative and false-negative findings in CE-MARC groups were compared by using the Fisher exact test.

Results

The spleen was visible in 99% (198 of 200) of examinations and interobserver agreement in the visual grading of splenic switch-off was excellent (κ = 0.92). Visually, splenic switch-off occurred in 90% of adenosine studies, but never in dobutamine or regadenoson studies. Semiquantitative assessments supported these observations: peak signal intensity was 78% less with adenosine than at rest (P < .001), but unchanged with regadenoson (4% reduction; P = .08). Calculated peak splenic divided by myocardial signal intensity (peak splenic/myocardial signal intensity) differed between stress agents (adenosine median, 0.34; dobutamine median, 1.34; regadenoson median, 1.13; P < .001). Failed splenic switch-off was significantly more common in CE-MARC patients with false-negative findings than with true-negative findings (34% vs 9%, P < .005).

Conclusion

Failed splenic switch-off with adenosine is a new, simple observation that identifies understressed patients who are at risk for false-negative findings on perfusion MR images. These data suggest that almost 10% of all patients may be understressed, and that repeat examination of individuals with failed splenic switch-off may significantly improve test sensitivity.
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Left Ventricular Noncompaction: A Clinically Useful Diagnostic Label?

Issue 8 Vol 8 Published on 2015-08-01 PMID 26271090 PMCID N/A
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Keywords: MRI, Prognosis, Dilated cardiomyopathy, Noncompaction
DOI: https://doi.org/10.1016/j.jcmg.2015.04.014
Authors: Steffen E Petersen In X
Abstract: No Abstract Available
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Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

Open Access Issue N/A Vol 17 Published on 2015-08-01 PMID 26264919 PMCID PMC4534050
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DOI: https://doi.org/10.1186/s12968-015-0176-3
Authors: Thomas A Treibel In X Filip Zemrak In X Daniel M Sado In X Sanjay M Banypersad In X Steven K White In X Viviana Maestrini In X Andrea Barison In X Vimal Patel In X Anna S Herrey In X Ceri Davies In X Mark J Caulfield In X Steffen E Petersen In X James C Moon In X
Abstract:

Background

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.

Methods

In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.

Results

Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m(2); female > 78 g/m(2)). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).

Conclusion

In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.
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Functional System and Areal Organization of a Highly Sampled Individual Human Brain.

Issue 3 Vol 87 Published on 2015-08-01 PMID 26212711 PMCID PMC4642864
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DOI: https://doi.org/10.1016/j.neuron.2015.06.037
Authors: Timothy O Laumann In X Evan M Gordon In X Babatunde Adeyemo In X Abraham Z Snyder In X Sung Jun Joo In X Mei-Yen Chen In X Adrian W Gilmore In X Kathleen B McDermott In X Steven M Nelson In X Nico U F Dosenbach In X Bradley L Schlaggar In X Jeanette A Mumford In X Russell A Poldrack In X Steven E Petersen In X
Abstract: Resting state functional MRI (fMRI) has enabled description of group-level functional brain organization at multiple spatial scales. However, cross-subject averaging may obscure patterns of brain organization specific to each individual. Here, we characterized the brain organization of a single individual repeatedly measured over more than a year. We report a reproducible and internally valid subject-specific areal-level parcellation that corresponds with subject-specific task activations. Highly convergent correlation network estimates can be derived from this parcellation if sufficient data are collected-considerably more than typically acquired. Notably, within-subject correlation variability across sessions exhibited a heterogeneous distribution across the cortex concentrated in visual and somato-motor regions, distinct from the pattern of intersubject variability. Further, although the individual's systems-level organization is broadly similar to the group, it demonstrates distinct topological features. These results provide a foundation for studies of individual differences in cortical organization and function, especially for special or rare individuals. VIDEO ABSTRACT.
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Visceral adiposity and left ventricular remodeling: The Multi-Ethnic Study of Atherosclerosis.

Issue 7 Vol 25 Published on 2015-07-01 PMID 26033394 PMCID PMC4468023
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Keywords: Obesity, Remodeling, Cardiac Magnetic Resonance Imaging, Visceral Adiposity
DOI: https://doi.org/10.1016/j.numecd.2015.03.016
Authors: S A Abbasi In X W G Hundley In X D A Bluemke In X M Jerosch-Herold In X R Blankstein In X Steffen E Petersen In X Oliver J Rider In X J A C Lima In X M A Allison In X V L Murthy In X R V Shah In X
Abstract:

Background and aims

Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods and results

We performed a post-hoc analysis on 1151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm(2)/m) with height-indexed LV mass (per height(2.7)) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ = 0.36 and 0.12, P < 0.0001, respectively), while only VF area was associated with LVMV (ρ = 0.28, P < 0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes.

Conclusion

Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted.
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Different Imaging Strategies in Patients With Possible Basilar Artery Occlusion: Cost-Effectiveness Analysis.

Open Access Issue 7 Vol 46 Published on 2015-07-01 PMID 26022634 PMCID PMC4476845
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Keywords: Stroke, Economics, Cost-effectiveness Analysis
DOI: https://doi.org/10.1161/strokeaha.115.008841
Authors: Sebastian E Beyer In X Myriam G Hunink In X Florian Schöberl In X Louisa von Baumgarten In X Steffen E Petersen In X Martin Dichgans In X Hendrik Janssen In X Birgit Ertl-Wagner In X Maximilian F Reiser In X Wieland H Sommer In X
Abstract:

Background and purpose

This study evaluated the cost-effectiveness of different noninvasive imaging strategies in patients with possible basilar artery occlusion.

Methods

A Markov decision analytic model was used to evaluate long-term outcomes resulting from strategies using computed tomographic angiography (CTA), magnetic resonance imaging, nonenhanced CT, or duplex ultrasound with intravenous (IV) thrombolysis being administered after positive findings. The analysis was performed from the societal perspective based on US recommendations. Input parameters were derived from the literature. Costs were obtained from United States costing sources and published literature. Outcomes were lifetime costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net monetary benefits, with a willingness-to-pay threshold of $80,000 per QALY. The strategy with the highest net monetary benefit was considered the most cost-effective. Extensive deterministic and probabilistic sensitivity analyses were performed to explore the effect of varying parameter values.

Results

In the reference case analysis, CTA dominated all other imaging strategies. CTA yielded 0.02 QALYs more than magnetic resonance imaging and 0.04 QALYs more than duplex ultrasound followed by CTA. At a willingness-to-pay threshold of $80,000 per QALY, CTA yielded the highest net monetary benefits. The probability that CTA is cost-effective was 96% at a willingness-to-pay threshold of $80,000/QALY. Sensitivity analyses showed that duplex ultrasound was cost-effective only for a prior probability of ≤0.02 and that these results were only minimally influenced by duplex ultrasound sensitivity and specificity. Nonenhanced CT and magnetic resonance imaging never became the most cost-effective strategy.

Conclusions

Our results suggest that CTA in patients with possible basilar artery occlusion is cost-effective.
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EuroEcho-Imaging 2014: highlights.

Issue 7 Vol 16 Published on 2015-07-01 PMID 25920925 PMCID N/A
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Keywords: Congenital heart disease, Heart valve disease, Heart Failure, Nuclear Cardiology, Cardiac Computed Tomography, Cardiac Magnetic Resonance, 3d Echocardiography
DOI: https://doi.org/10.1093/ehjci/jev084
Authors: Julien Magne In X Gilbert Habib In X Bernard Cosyns In X Erwan Donal In X Owen Miller In X Danilo Neglia In X Steffen E Petersen In X Patrizio Lancellotti In X
Abstract: The annual meeting of the European Association of Echocardiography (EuroEcho-Imaging) was held in Vienna, Austria. In the present paper, we present a summary of the 'Highlights' session.
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Brief Report: Theory of Mind, Relational Reasoning, and Social Responsiveness in Children With and Without Autism: Demonstration of Feasibility for a Larger-Scale Study.

Issue 7 Vol 45 Published on 2015-07-01 PMID 25630898 PMCID PMC4474755
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DOI: https://doi.org/10.1007/s10803-015-2357-1
Authors: John R Pruett In X Sridhar Kandala In X Steven E Petersen In X Daniel J Povinelli In X
Abstract: Understanding the underpinnings of social responsiveness and theory of mind (ToM) will enhance our knowledge of autism spectrum disorder (ASD). We hypothesize that higher-order relational reasoning (higher-order RR: reasoning necessitating integration of relationships among multiple variables) is necessary but not sufficient for ToM, and that social responsiveness varies independently of higher-order RR. A pilot experiment tested these hypotheses in n = 17 children, 3-14, with and without ASD. No child failing 2nd-order RR passed a false belief ToM test. Contrary to prediction, Social Responsiveness Scale scores did correlate with 2nd-order RR performance, likely due to sample characteristics. It is feasible to translate this comparative cognition-inspired line of inquiry for full-scale studies of ToM, higher-order RR, and social responsiveness in ASD.
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Separable roles for attentional control sub-systems in reading tasks: a combined behavioral and fMRI study.

Open Access Issue 5 Vol 25 Published on 2015-05-01 PMID 24275830 PMCID PMC4397571
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Keywords: Regularity, Phonology, Orthography, Dual Route, Lexicality
DOI: https://doi.org/10.1093/cercor/bht313
Authors: S K Z Ihnen In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Attentional control is important both for learning to read and for performing difficult reading tasks. A previous study invoked 2 mechanisms to explain reaction time (RT) differences between reading tasks with variable attentional demands. The present study combined behavioral and neuroimaging measures to test the hypotheses that there are 2 mechanisms of interaction between attentional control and reading; that these mechanisms are dissociable both behaviorally and neuro-anatomically; and that the 2 mechanisms involve functionally separable control systems. First, RT evidence was found in support of the 2-mechanism model, corroborating the previous study. Next, 2 sets of brain regions were identified as showing functional magnetic resonance imaging blood oxygen level-dependent activity that maps onto the 2-mechanism distinction. One set included bilateral Cingulo-opercular regions and mostly right-lateralized Dorsal Attention regions (CO/DA+). This CO/DA+ region set showed response properties consistent with a role in reporting which processing pathway (phonological or lexical) was biased for a particular trial. A second set was composed primarily of left-lateralized Frontal-parietal (FP) regions. Its signal properties were consistent with a role in response checking. These results demonstrate how the subcomponents of attentional control interact with subcomponents of reading processes in healthy young adults.
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The optimal imaging strategy for patients with stable chest pain: a cost-effectiveness analysis.

Issue 7 Vol 162 Published on 2015-04-01 PMID 25844996 PMCID N/A
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Keywords:
DOI: https://doi.org/10.7326/m14-0027
Authors: Tessa S S Genders In X Steffen E Petersen In X Francesca Pugliese In X Amardeep G Dastidar In X Kirsten E Fleischmann In X Koen Nieman In X M G Myriam Hunink In X
Abstract:

Background

The optimal imaging strategy for patients with stable chest pain is uncertain.

Objective

To determine the cost-effectiveness of different imaging strategies for patients with stable chest pain.

Design

Microsimulation state-transition model.

Data sources

Published literature.

Target population

60-year-old patients with a low to intermediate probability of coronary artery disease (CAD).

Time horizon

Lifetime.

Perspective

The United States, the United Kingdom, and the Netherlands.

Intervention

Coronary computed tomography (CT) angiography, cardiac stress magnetic resonance imaging, stress single-photon emission CT, and stress echocardiography.

Outcome measures

Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.

Results of base-case analysis

The strategy that maximized QALYs and was cost-effective in the United States and the Netherlands began with coronary CT angiography, continued with cardiac stress imaging if angiography found at least 50% stenosis in at least 1 coronary artery, and ended with catheter-based coronary angiography if stress imaging induced ischemia of any severity. For U.K. men, the preferred strategy was optimal medical therapy without catheter-based coronary angiography if coronary CT angiography found only moderate CAD or stress imaging induced only mild ischemia. In these strategies, stress echocardiography was consistently more effective and less expensive than other stress imaging tests. For U.K. women, the optimal strategy was stress echocardiography followed by catheter-based coronary angiography if echocardiography induced mild or moderate ischemia.

Results of sensitivity analysis

Results were sensitive to changes in the probability of CAD and assumptions about false-positive results.

Limitations

All cardiac stress imaging tests were assumed to be available. Exercise electrocardiography was included only in a sensitivity analysis. Differences in QALYs among strategies were small.

Conclusion

Coronary CT angiography is a cost-effective triage test for 60-year-old patients who have nonacute chest pain and a low to intermediate probability of CAD.

Primary funding source

Erasmus University Medical Center.
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Accurate age classification of 6 and 12 month-old infants based on resting-state functional connectivity magnetic resonance imaging data.

Open Access Issue N/A Vol 12 Published on 2015-04-01 PMID 25704288 PMCID PMC4385423
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Keywords: Development, Infant, Support vector machine (SVM), Functional Brain Networks, Multivariate Pattern Analysis (Mvpa), Functional Connectivity Magnetic Resonance Imaging (Fcmri)
DOI: https://doi.org/10.1016/j.dcn.2015.01.003
Authors: John R Pruett In X Sridhar Kandala In X Sarah Hoertel In X Abraham Z Snyder In X Jed T Elison In X Tomoyuki Nishino In X Eric Feczko In X Nico U F Dosenbach In X Binyam Nardos In X Jonathan D Power In X Babatunde Adeyemo In X Kelly N Botteron In X Robert C McKinstry In X Alan C Evans In X Heather C Hazlett In X Stephen R Dager In X Sarah Paterson In X Robert T Schultz In X D Louis Collins In X Vladimir S Fonov In X Martin Styner In X Guido Gerig In X Samir Das In X Penelope Kostopoulos In X John N Constantino In X Annette M Estes In X In X Steven E Petersen In X Bradley L Schlaggar In X Joseph Piven In X
Abstract: Human large-scale functional brain networks are hypothesized to undergo significant changes over development. Little is known about these functional architectural changes, particularly during the second half of the first year of life. We used multivariate pattern classification of resting-state functional connectivity magnetic resonance imaging (fcMRI) data obtained in an on-going, multi-site, longitudinal study of brain and behavioral development to explore whether fcMRI data contained information sufficient to classify infant age. Analyses carefully account for the effects of fcMRI motion artifact. Support vector machines (SVMs) classified 6 versus 12 month-old infants (128 datasets) above chance based on fcMRI data alone. Results demonstrate significant changes in measures of brain functional organization that coincide with a special period of dramatic change in infant motor, cognitive, and social development. Explorations of the most different correlations used for SVM lead to two different interpretations about functional connections that support 6 versus 12-month age categorization.
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The multi-modality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging.

Issue 4 Vol 16 Published on 2015-04-01 PMID 25681828 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1093/ehjci/jeu323
Authors: Maurizio Galderisi In X Nuno Cardim In X Antonello D'Andrea In X Oliver Bruder In X Bernard Cosyns In X Laurent Davin In X Erwan Donal In X Thor Edvardsen In X Antonio Freitas In X Gilbert Habib In X Anastasia Kitsiou In X Sven Plein In X Steffen E Petersen In X Bogdan A Popescu In X Stephen Schroeder In X Christof Burgstahler In X Patrizio Lancellotti In X
Abstract: The term 'athlete's heart' refers to a clinical picture characterized by a slow heart rate and enlargement of the heart. A multi-modality imaging approach to the athlete's heart aims to differentiate physiological changes due to intensive training in the athlete's heart from serious cardiac diseases with similar morphological features. Imaging assessment of the athlete's heart should begin with a thorough echocardiographic examination.Left ventricular (LV) wall thickness by echocardiography can contribute to the distinction between athlete's LV hypertrophy and hypertrophic cardiomyopathy (HCM). LV end-diastolic diameter becomes larger (>55 mm) than the normal limits only in end-stage HCM patients when the LV ejection fraction is <50%. Patients with HCM also show early impairment of LV diastolic function, whereas athletes have normal diastolic function.When echocardiography cannot provide a clear differential diagnosis, cardiac magnetic resonance (CMR) imaging should be performed.With CMR, accurate morphological and functional assessment can be made. Tissue characterization by late gadolinium enhancement may show a distinctive, non-ischaemic pattern in HCM and a variety of other myocardial conditions such as idiopathic dilated cardiomyopathy or myocarditis. The work-up of athletes with suspected coronary artery disease should start with an exercise ECG. In athletes with inconclusive exercise ECG results, exercise stress echocardiography should be considered. Nuclear cardiology techniques, coronary cardiac tomography (CCT) and/or CMR may be performed in selected cases. Owing to radiation exposure and the young age of most athletes, the use of CCT and nuclear cardiology techniques should be restricted to athletes with unclear stress echocardiography or CMR.
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Analysis of cortical shape in children with simplex autism.

Issue 4 Vol 25 Published on 2015-04-01 PMID 24165833 PMCID PMC4366616
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Keywords: Morphometry, Asd, Movies, Sulcal Depth, Simplex Autism, Surface-based
DOI: https://doi.org/10.1093/cercor/bht294
Authors: Donna L Dierker In X Eric Feczko In X John R Pruett In X Steven E Petersen In X Bradley L Schlaggar In X John N Constantino In X John W Harwell In X Timothy S Coalson In X David C Van Essen In X
Abstract: We used surface-based morphometry to test for differences in cortical shape between children with simplex autism (n = 34, mean age 11.4 years) and typical children (n = 32, mean age 11.3 years). This entailed testing for group differences in sulcal depth and in 3D coordinates after registering cortical midthickness surfaces to an atlas target using 2 independent registration methods. We identified bilateral differences in sulcal depth in restricted portions of the anterior-insula and frontal-operculum (aI/fO) and in the temporoparietal junction (TPJ). The aI/fO depth differences are associated with and likely to be caused by a shape difference in the inferior frontal gyrus in children with simplex autism. Comparisons of average midthickness surfaces of children with simplex autism and those of typical children suggest that the significant sulcal depth differences represent local peaks in a larger pattern of regional differences that are below statistical significance when using coordinate-based analysis methods. Cortical regions that are statistically significant before correction for multiple measures are peaks of more extended, albeit subtle regional differences that may guide hypothesis generation for studies using other imaging modalities.
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Role of multimodality cardiac imaging in the management of patients with hypertrophic cardiomyopathy: an expert consensus of the European Association of Cardiovascular Imaging Endorsed by the Saudi Heart Association.

Issue 3 Vol 16 Published on 2015-03-01 PMID 25650407 PMCID N/A
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Keywords: Echocardiography, hypertrophic cardiomyopathy, Left ventricular hypertrophy, Cardiac Computed Tomography, Cardiac Magnetic Resonance, Multimodality Imaging, Cardiac Nuclear Imaging
DOI: https://doi.org/10.1093/ehjci/jeu291
Authors: Nuno Cardim In X Maurizio Galderisi In X Thor Edvardsen In X Sven Plein In X Bogdan A Popescu In X Antonello D'Andrea In X Oliver Bruder In X Bernard Cosyns In X Laurent Davin In X Erwan Donal In X Antonio Freitas In X Gilbert Habib In X Anastasia Kitsiou In X Steffen E Petersen In X Stephen Schroeder In X Patrizio Lancellotti In X Paolo Camici In X Raluca Dulgheru In X Andreas Hagendorff In X Massimo Lombardi In X Denisa Muraru In X Rosa Sicari In X
Abstract: Taking into account the complexity and limitations of clinical assessment in hypertrophic cardiomyopathy (HCM), imaging techniques play an essential role in the evaluation of patients with this disease. Thus, in HCM patients, imaging provides solutions for most clinical needs, from diagnosis to prognosis and risk stratification, from anatomical and functional assessment to ischaemia detection, from metabolic evaluation to monitoring of treatment modalities, from staging and clinical profiles to follow-up, and from family screening and preclinical diagnosis to differential diagnosis. Accordingly, a multimodality imaging (MMI) approach (including echocardiography, cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging) is encouraged in the assessment of these patients. The choice of which technique to use should be based on a broad perspective and expert knowledge of what each technique has to offer, including its specific advantages and disadvantages. Experts in different imaging techniques should collaborate and the different methods should be seen as complementary, not as competitors. Each test must be selected in an integrated and rational way in order to provide clear answers to specific clinical questions and problems, trying to avoid redundant and duplicated information, taking into account its availability, benefits, risks, and cost.
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Myocardial tissue phase mapping reveals impaired myocardial tissue velocities in obesity.

Issue 2 Vol 31 Published on 2015-02-01 PMID 25301275 PMCID N/A
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DOI: https://doi.org/10.1007/s10554-014-0548-z
Authors: Oliver J Rider In X Ezimamaka Ajufo In X Mohammed K Ali In X Steffen E Petersen In X Richard Nethononda In X Jane M Francis In X Stefan Neubauer In X
Abstract: Although obesity is linked to heart failure on a population level, not all obese subjects develop cardiac failure. As a result, identifying obese subjects with subclinical changes in myocardial velocities may enable earlier detection of those susceptible to developing overt heart failure. As echocardiography is limited in obesity due to limited acoustic window, we used phase contrast magnetic resonance imaging to assess myocardial velocities in obese and normal weight subjects. Normal weight (BMI 23 ± 3; n = 40) and obese subjects (BMI 37 ± 7; n = 59) without identifiable cardiovascular risk factors underwent MRI (1.5 Tesla) to determine left ventricular myocardial velocities using phase contrast tissue phase mapping. Systolic function was not different between normal and obese subjects (LVEF 67 ± 5 vs 68 ± 4, p = 0.22). However, obesity was associated with significantly impaired peak radial and longitudinal diastolic myocardial velocity (by 13 and 19 % respectively, both p < 0.001). In addition time-to-peak longitudinal diastolic velocity was delayed in obesity (by 39 ms, p < 0.001). In addition, peak longitudinal diastolic strain was 20 % lower in obesity (p = 0.015) and time-to-peak longitudinal diastolic strain rate significantly delayed in obesity (by 92 ms, p < 0.001).Although peak radial systolic velocity was similar between obese and normal weight subjects (p = 0.14) peak longitudinal systolic velocity was 7 % lower in the obese cohort (p = 0.02). In obesity without co-morbidities, tissue phase mapping has shown subclinical changes in systolic and diastolic function. Given the link between obesity and heart failure, early detection of changes may become clinically important to prevent disease progression.
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"3D fusion" echocardiography improves 3D left ventricular assessment: comparison with 2D contrast echocardiography.

Issue 2 Vol 32 Published on 2015-02-01 PMID 24924997 PMCID N/A
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Keywords: Image fusion, Echocardiography, contrast, 3d
DOI: https://doi.org/10.1111/echo.12655
Authors: Daniel Augustine In X Mohammad Yaqub In X Cezary Szmigielski In X Eduardo Lima In X Steffen E Petersen In X Harald Becher In X J Alison Noble In X Paul Leeson In X
Abstract:

Background

Three-dimensional fusion echocardiography (3DFE) is a novel postprocessing approach that utilizes imaging data acquired from multiple 3D acquisitions. We assessed image quality, endocardial border definition, and cardiac wall motion in patients using 3DFE compared to standard 3D images (3D) and results obtained with contrast echocardiography (2DC).

Methods

Twenty-four patients (mean age 66.9 ± 13 years, 17 males, 7 females) undergoing 2DC had three, noncontrast, 3D apical volumes acquired at rest. Images were fused using an automated image fusion approach. Quality of the 3DFE was compared to both 3D and 2DC based on contrast-to-noise ratio (CNR) and endocardial border definition. We then compared clinical wall-motion score index (WMSI) calculated from 3DFE and 3D to those obtained from 2DC images.

Results

Fused 3D volumes had significantly improved CNR (8.92 ± 1.35 vs. 6.59 ± 1.19, P < 0.0005) and segmental image quality (2.42 ± 0.99 vs. 1.93 ± 1.18, P < 0.005) compared to unfused 3D acquisitions. Levels achieved were closer to scores for 2D contrast images (CNR: 9.04 ± 2.21, P = 0.6; segmental image quality: 2.91 ± 0.37, P < 0.005). WMSI calculated from fused 3D volumes did not differ significantly from those obtained from 2D contrast echocardiography (1.06 ± 0.09 vs. 1.07 ± 0.15, P = 0.69), whereas unfused images produced significantly more variable results (1.19 ± 0.30). This was confirmed by a better intraclass correlation coefficient (ICC 0.72; 95% CI 0.32-0.88) relative to comparisons with unfused images (ICC 0.56; 95% CI 0.02-0.81).

Conclusion

3DFE significantly improves left ventricular image quality compared to unfused 3D in a patient population and allows noncontrast assessment of wall motion that approaches that achieved with 2D contrast echocardiography.
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Relationships between dose to the gastro-intestinal tract and patient-reported symptom domains after radiotherapy for localized prostate cancer.

Issue 9 Vol 54 Published on 2015-01-01 PMID 26340136 PMCID PMC4786008
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DOI: https://doi.org/10.3109/0284186x.2015.1063779
Authors: Maria Thor In X Caroline E Olsson In X Jung Hun Oh In X Stine E Petersen In X David Alsadius In X Lise Bentzen In X Niclas Pettersson In X Ludvig P Muren In X Ann-Charlotte Waldenström In X Morten Høyer In X Gunnar Steineck In X Joseph O Deasy In X
Abstract:

Background

Gastrointestinal (GI) morbidity after radiotherapy (RT) for prostate cancer is typically addressed by studying specific single symptoms. The aim of this study was to explore the interplay between domains of patient- reported outcomes (PROs) on GI morbidity, and to what extent these are explained by RT dose to the GI tract.

Material and methods

The study included men from two Scandinavian studies (N = 211/277) who had undergone primary external beam radiotherapy (EBRT) for localized prostate cancer to 70-78 Gy (2 Gy/fraction). Factor analysis was applied to previously identified PRO-based symptom domains from two study-specific questionnaires. Number of questions: 43; median time to follow-up: 3.6-6.4 years) and dose-response outcome variables were defined from these domains. Dose/volume parameters of the anal sphincter (AS) or the rectum were tested as predictors for each outcome variable using logistic regression with 10-fold cross-validation. Performance was assessed using area under the receiver operating characteristic curve (Az) and model frequency.

Results

Outcome variables from Defecation urgency (number of symptoms: 2-3), Fecal leakage (4-6), Mucous (4), and Pain (3-6) were defined. In both cohorts, intermediate rectal doses predicted Defecation urgency (mean Az: 0.53-0.54; Frequency: 70-75%), and near minimum and low AS doses predicted Fecal leakage (mean Az: 0.63-0.67; Frequency: 83-99%). In one cohort, high AS doses predicted Mucous (mean Az: 0.54; Frequency: 96%), whereas in the other, low AS doses and intermediate rectal doses predicted Pain (mean Az: 0.69; Frequency: 28-82%).

Conclusion

We have demonstrated that Defecation urgency, Fecal leakage, Mucous, and Pain following primary EBRT for localized prostate cancer primarily are predicted by intermediate rectal doses, low AS doses, high AS doses, or a combination of low AS and intermediate rectal doses, respectively. This suggests that there is a domain-specific dose-response for the GI tract. To reduce risk of GI morbidity, dose distributions of both the AS region and the rectum should, therefore, be considered when prescribing prostate cancer RT.
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The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

Open Access Issue N/A Vol 13 Published on 2015-01-01 PMID 25637245 PMCID PMC4311412
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DOI: https://doi.org/10.1186/s12916-014-0265-4
Authors: Peter Croft In X Douglas G Altman In X Jonathan J Deeks In X Kate M Dunn In X Alastair D Hay In X Harry Hemingway In X Linda LeResche In X George Peat In X Pablo Perel In X Steffen E Petersen In X Richard D Riley In X Ian Roberts In X Michael Sharpe In X Richard J Stevens In X Danielle A Van Der Windt In X Michael Von Korff In X Adam Timmis In X
Abstract:

Background

Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful.

Discussion

Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome.

Summary

Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care.
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Spatial and temporal characteristics of error-related activity in the human brain.

Issue 1 Vol 35 Published on 2015-01-01 PMID 25568119 PMCID PMC4287146
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Keywords: Error, Meta-analysis, Resting state, Functional Networks, Task Control
DOI: https://doi.org/10.1523/jneurosci.1313-14.2015
Authors: Maital Neta In X Francis M Miezin In X Steven M Nelson In X Joseph W Dubis In X Nico U F Dosenbach In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: A number of studies have focused on the role of specific brain regions, such as the dorsal anterior cingulate cortex during trials on which participants make errors, whereas others have implicated a host of more widely distributed regions in the human brain. Previous work has proposed that there are multiple cognitive control networks, raising the question of whether error-related activity can be found in each of these networks. Thus, to examine error-related activity broadly, we conducted a meta-analysis consisting of 12 tasks that included both error and correct trials. These tasks varied by stimulus input (visual, auditory), response output (button press, speech), stimulus category (words, pictures), and task type (e.g., recognition memory, mental rotation). We identified 41 brain regions that showed a differential fMRI BOLD response to error and correct trials across a majority of tasks. These regions displayed three unique response profiles: (1) fast, (2) prolonged, and (3) a delayed response to errors, as well as a more canonical response to correct trials. These regions were found mostly in several control networks, each network predominantly displaying one response profile. The one exception to this "one network, one response profile" observation is the frontoparietal network, which showed prolonged response profiles (all in the right hemisphere), and fast profiles (all but one in the left hemisphere). We suggest that, in the place of a single localized error mechanism, these findings point to a large-scale set of error-related regions across multiple systems that likely subserve different functions.
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Obese subjects show sex-specific differences in right ventricular hypertrophy.

Issue 1 Vol 8 Published on 2015-01-01 PMID 25552492 PMCID N/A
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Keywords: Sex, Obesity, diastole, Hypertrophy, Right Ventricular
DOI: https://doi.org/10.1161/circimaging.114.002454
Authors: Oliver J Rider In X Andrew J M Lewis In X Adam J Lewandowski In X Ntobeko Ntusi In X Richard Nethononda In X Steffen E Petersen In X Jane M Francis In X Alex Pitcher In X Rajarshi Banerjee In X Paul Leeson In X Stefan Neubauer In X
Abstract:

Background

As right ventricular (RV) remodeling in obesity remains underinvestigated, and the impact of left ventricular (LV) diastolic dysfunction on RV hypertrophy is unknown, we aimed to investigate whether (1) sex-specific patterns of RV remodeling exist in obesity and (2) LV diastolic dysfunction in obesity is related to RV hypertrophy.

Methods and results

Seven hundred thirty-nine subjects (women, n=345; men, n=394) without identifiable cardiovascular risk factors (body mass index [BMI], 15.3-59.2 kg/m2) underwent cardiovascular magnetic resonance (1.5 T) to measure RV mass (g), RV end-diastolic volume (mL), RV mass/volume ratio, and LV diastolic peak filling rate (mL/s). All subjects were normotensive (average, 119±11/73±8 mm Hg), normoglycaemic (4.8±0.5 mmol/L), and normocholesterolaemic (4.8±0.9 mmol/L) at the time of scanning. Across both sexes, there was a moderately strong positive correlation between BMI and RV mass (men, +0.8 g per BMI point increase; women, +1.0 g per BMI point increase; both P<0.001). Whereas women exhibited RV cavity dilatation (RV end-diastolic volume, +1.0 mL per BMI point increase; P<0.001), BMI was not correlated with RV end-diastolic volume in men (R=0.04; P=0.51). Concentric RV remodeling was present in both sexes, with RV mass/volume ratio being positively correlated to BMI (men, R=0.41; women, R=0.51; both P<0.001). Irrespective of sex, the LV peak filling rate was negatively correlated with both RV mass (men, R=-0.43; women, R=-0.44; both P<0.001) and RV mass/volume ratio (men, R=-0.37; women, R=-0.35; both P<0.001).

Conclusions

A sex difference in RV remodeling exists in obesity. Whereas men exhibit concentric RV remodeling, women exhibit a mixed pattern of eccentric and concentric remodeling. Regardless of sex, reduced LV diastolic function is associated with concentric RV remodeling.
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Recent progress and outstanding issues in motion correction in resting state fMRI.

Issue N/A Vol 105 Published on 2015-01-01 PMID 25462692 PMCID PMC4262543
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Keywords: fMRI, Motion, Resting state, Denoising, Functional Connectivity, Artifact
DOI: https://doi.org/10.1016/j.neuroimage.2014.10.044
Authors: Jonathan D Power In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The purpose of this review is to communicate and synthesize recent findings related to motion artifact in resting state fMRI. In 2011, three groups reported that small head movements produced spurious but structured noise in brain scans, causing distance-dependent changes in signal correlations. This finding has prompted both methods development and the re-examination of prior findings with more stringent motion correction. Since 2011, over a dozen papers have been published specifically on motion artifact in resting state fMRI. We will attempt to distill these papers to their most essential content. We will point out some aspects of motion artifact that are easily or often overlooked. Throughout the review, we will highlight gaps in current knowledge and avenues for future research.
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Simplifying cardiovascular magnetic resonance pulse sequence terminology.

Open Access Issue N/A Vol 16 Published on 2014-12-01 PMID 25551695 PMCID PMC4280685
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DOI: https://doi.org/10.1186/s12968-014-0103-z
Authors: Matthias G Friedrich In X Chiara Bucciarelli-Ducci In X James A White In X Sven Plein In X James C Moon In X Ana G Almeida In X Christopher M Kramer In X Stefan Neubauer In X Dudley J Pennell In X Steffen E Petersen In X Raymond Y Kwong In X Victor A Ferrari In X Jeanette Schulz-Menger In X Hajime Sakuma In X Erik B Schelbert In X Éric Larose In X Ingo Eitel In X Iacopo Carbone In X Andrew J Taylor In X Alistair Young In X Albert de Roos In X Eike Nagel In X
Abstract: We propose a set of simplified terms to describe applied Cardiovascular Magnetic Resonance (CMR) pulse sequence techniques in clinical reports, scientific articles and societal guidelines or recommendations. Rather than using various technical details in clinical reports, the description of the technical approach should be based on the purpose of the pulse sequence. In scientific papers or other technical work, this should be followed by a more detailed description of the pulse sequence and settings. The use of a unified set of widely understood terms would facilitate the communication between referring physicians and CMR readers by increasing the clarity of CMR reports and thus improve overall patient care. Applied in research articles, its use would facilitate non-expert readers' understanding of the methodology used and its clinical meaning.
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Studying brain organization via spontaneous fMRI signal.

Issue 4 Vol 84 Published on 2014-11-01 PMID 25459408 PMCID PMC4254503
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DOI: https://doi.org/10.1016/j.neuron.2014.09.007
Authors: Jonathan D Power In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the "resting" brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called "resting state." This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization.
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The relationship of left ventricular trabeculation to ventricular function and structure over a 9.5-year follow-up: the MESA study.

Issue 19 Vol 64 Published on 2014-11-01 PMID 25440091 PMCID PMC4610345
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Keywords: left ventricular function, Cardiac Magnetic Resonance, Left Ventricular Trabeculations
DOI: https://doi.org/10.1016/j.jacc.2014.08.035
Authors: Filip Zemrak In X Mark A Ahlman In X Gabriella Captur In X Saidi A Mohiddin In X Nadine Kawel-Boehm In X Martin R Prince In X James C Moon In X William G Hundley In X João A C Lima In X David A Bluemke In X Steffen E Petersen In X
Abstract:

Background

Left ventricular (LV) trabeculation is highly variable among individuals and is increased in some diseases (e.g., congenital heart disease or cardiomyopathies), but its significance in population-representative individuals is unknown.

Objectives

The goal of this study was to determine if excessive LV trabeculation in population-representative individuals is associated with preceding changes in cardiac volumes and function.

Methods

For technical reasons, the extent of trabeculation, which is expressed as the ratio of noncompacted to compacted (NC/C) myocardium, was measured on cardiac magnetic resonance (CMR) long-axis cine images in 2,742 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (mean age 68.7 years; 52.3% women; 56.4% with hypertension; 16.8% with diabetes) at examination 5. These were considered in quintiles of trabeculation extent; the NC/C ratio of quintile 5 was 2.46 to 5.41. We determined the relationship between the maximal NC/C ratio and the preceding change (9.5 years between examinations 1 and 5) in end-systolic volume indexed (ESVi) to body surface area. Secondary analyses assessed the associations between the maximal NC/C ratio and preceding changes in end-diastolic volume indexed (EDVi) to body surface area and the ejection fraction (EF).

Results

Over 9.5 years, the ESVi decreased by 1.3 ml/m(2), the EDVi decreased by 5.1 ml/m(2), and the EF decreased by 0.6% (p < 0.0001). Even in subjects with excessive trabeculation, there were no clinically relevant differences in LV volumes and systolic function changes among the quintiles of trabeculation extent.

Conclusions

Greater extent of, and even excessive, LV trabeculation measured in end-diastole in asymptomatic population-representative individuals appeared benign and was not associated with deterioration in LV volumes or function during an almost 10-year period.
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Decreased segregation of brain systems across the healthy adult lifespan.

Issue 46 Vol 111 Published on 2014-11-01 PMID 25368199 PMCID PMC4246293
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Keywords: Aging, Memory, Connectome, Brain Networks, Resting-state Correlations
DOI: https://doi.org/10.1073/pnas.1415122111
Authors: Micaela Y Chan In X Denise C Park In X Neil K Savalia In X Steven E Petersen In X Gagan S Wig In X
Abstract: Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age.
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Pathophysiology of late anorectal dysfunction following external beam radiotherapy for prostate cancer.

Issue 10 Vol 53 Published on 2014-10-01 PMID 24960583 PMCID N/A
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Keywords:
DOI: https://doi.org/10.3109/0284186x.2014.926029
Authors: Stine E Petersen In X Sidse Bregendahl In X Maria Langschwager In X Søren Laurberg In X Christina Brock In X Asbjørn M Drewes In X Klaus Krogh In X Morten Høyer In X Lilli Lundby In X
Abstract:

Background

Patients treated with external beam radiotherapy (EBRT) may suffer from long-term anorectal adverse effects. The purpose of the present study was to assess long-term functional and structural anorectal changes in patients previously treated with EBRT for prostate cancer and to suggest the mechanism behind the development of the adverse effects.

Material and methods

Our previously proposed RT-induced anorectal dysfunction (RT-ARD) score, developed with the intention to survey anorectal dysfunction was used to identify patients with and without anorectal symptoms. Among 309 patients surveyed with the questionnaire, we chose 23 patients with the highest RT-ARD score and 19 patients with the lowest RT-ARD score. They were investigated by multimodal rectal sensory stimulation, standard anal physiological tests. Changes of the rectal mucosa were assessed by flexible sigmoidoscopy and graded by the Vienna Rectoscopy Score (VRS).

Results

The mean follow-up time was 3.8 (range, 2.8; 8.6) years in patients with high RT-ARD and 3.8 (range, 2.6; 5.9) in patients with low RT-ARD. Endoscopic evaluation revealed higher VRS scores in patients with high RT-ARD compared to patients with low RT-ARD (p = 0.002). Patients with high RT-ARD had increased rectal sensory response to distension manifested both as volume (p = 0.006) and cross-sectional area (p = 0.04), and they had reduced maximum anal resting pressure assessed by anal manometri (p = 0.02).

Conclusions

Long-term anorectal symptoms correlate to changes in anorectal biomechanical properties and rectal mucosal injury. Our data suggests that RT-induced long-term anorectal dysfunction is multifactorial caused by injury of the rectal mucosa and the internal anal sphincter combined with increased rectal sensitivity and reduced rectal functional capacity.
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Separable responses to error, ambiguity, and reaction time in cingulo-opercular task control regions.

Issue N/A Vol 99 Published on 2014-10-01 PMID 24887509 PMCID PMC4148211
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DOI: https://doi.org/10.1016/j.neuroimage.2014.05.053
Authors: Maital Neta In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The dorsal anterior cingulate (dACC), along with the closely affiliated anterior insula/frontal operculum, have been demonstrated to show three types of task control signals across a wide variety of tasks. One of these signals, a transient signal that is thought to represent performance feedback, shows greater activity to error than correct trials. Other work has found similar effects for uncertainty/ambiguity or conflict, though some argue that dACC activity is, instead, modulated primarily by other processes more reflected in reaction time. Here, we demonstrate that, rather than a single explanation, multiple information processing operations are crucial to characterizing the function of these brain regions, by comparing operations within a single paradigm. Participants performed two tasks in an fMRI experimental session: (1) deciding whether or not visually presented word pairs rhyme, and (2) rating auditorily presented single words as abstract or concrete. A pilot was used to identify ambiguous stimuli for both tasks (e.g., word pair: BASS/GRACE; single word: CHANGE). We found greater cingulo-opercular activity for errors and ambiguous trials than clear/correct trials, with a robust effect of reaction time. The effects of error and ambiguity remained when reaction time was regressed out, although the differences decreased. Further stepwise regression of response consensus (agreement across participants for each stimulus; a proxy for ambiguity) decreased differences between ambiguous and clear trials, but left error-related differences almost completely intact. These observations suggest that trial-wise responses in cingulo-opercular regions monitor multiple performance indices, including accuracy, ambiguity, and reaction time.
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Network measures predict neuropsychological outcome after brain injury.

Issue 39 Vol 111 Published on 2014-09-01 PMID 25225403 PMCID PMC4191760
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Keywords: fMRI, neuropsychology, Functional Connectivity, Brain Hubs
DOI: https://doi.org/10.1073/pnas.1322173111
Authors: David E Warren In X Jonathan D Power In X Joel Bruss In X Natalie L Denburg In X Eric J Waldron In X Haoxin Sun In X Steven E Petersen In X Daniel Tranel In X
Abstract: Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.
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Linking left ventricular function and mural architecture: what does the clinician need to know?

Issue 16 Vol 100 Published on 2014-08-01 PMID 24310520 PMCID N/A
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Keywords: Cardiac function, Basic Science
DOI: https://doi.org/10.1136/heartjnl-2013-304571
Authors: John B Partridge In X Morten H Smerup In X Steffen E Petersen In X Peter F Niederer In X Robert H Anderson In X
Abstract: No Abstract Available
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Parcellating an individual subject's cortical and subcortical brain structures using snowball sampling of resting-state correlations.

Open Access Issue 8 Vol 24 Published on 2014-08-01 PMID 23476025 PMCID PMC4089380
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Keywords: Individual Differences, Brain Networks, Snowball Sampling, Boundary Mapping, Resting-state Functional Correlations, Brain Area Parcellation
DOI: https://doi.org/10.1093/cercor/bht056
Authors: Gagan S Wig In X Timothy O Laumann In X Alexander L Cohen In X Jonathan D Power In X Steven M Nelson In X Matthew F Glasser In X Francis M Miezin In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: We describe methods for parcellating an individual subject's cortical and subcortical brain structures using resting-state functional correlations (RSFCs). Inspired by approaches from social network analysis, we first describe the application of snowball sampling on RSFC data (RSFC-Snowballing) to identify the centers of cortical areas, subdivisions of subcortical nuclei, and the cerebellum. RSFC-Snowballing parcellation is then compared with parcellation derived from identifying locations where RSFC maps exhibit abrupt transitions (RSFC-Boundary Mapping). RSFC-Snowballing and RSFC-Boundary Mapping largely complement one another, but also provide unique parcellation information; together, the methods identify independent entities with distinct functional correlations across many cortical and subcortical locations in the brain. RSFC parcellation is relatively reliable within a subject scanned across multiple days, and while the locations of many area centers and boundaries appear to exhibit considerable overlap across subjects, there is also cross-subject variability-reinforcing the motivation to parcellate brains at the level of individuals. Finally, examination of a large meta-analysis of task-evoked functional magnetic resonance imaging data reveals that area centers defined by task-evoked activity exhibit correspondence with area centers defined by RSFC-Snowballing. This observation provides important evidence for the ability of RSFC to parcellate broad expanses of an individual's brain into functionally meaningful units.
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Development and delivery of a high-quality European Cardiovascular Magnetic Resonance Examination.

Issue 25 Vol 35 Published on 2014-07-01 PMID 25118343 PMCID N/A
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DOI: #
Authors: Steffen E Petersen In X Sven Plein In X
Abstract: No Abstract Available
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Intrinsic and task-evoked network architectures of the human brain.

Issue 1 Vol 83 Published on 2014-07-01 PMID 24991964 PMCID PMC4082806
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DOI: https://doi.org/10.1016/j.neuron.2014.05.014
Authors: Michael W Cole In X Danielle S Bassett In X Jonathan D Power In X Todd S Braver In X Steven E Petersen In X
Abstract: Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an "intrinsic," standard architecture of functional brain organization. Furthermore, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain's functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity-areas of neuroscientific inquiry typically considered separately.
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Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer.

Issue 14 Vol 59 Published on 2014-07-01 PMID 24936956 PMCID PMC4786025
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DOI: https://doi.org/10.1088/0031-9155/59/14/3749
Authors: C Olsson In X M Thor In X M Liu In X V Moissenko In X S E Petersen In X M Høyer In X A Apte In X J O Deasy In X
Abstract: When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.
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Update of the European Association of Cardiovascular Imaging (EACVI) Core Syllabus for the European Cardiovascular Magnetic Resonance Certification Exam.

Issue 7 Vol 15 Published on 2014-07-01 PMID 24855220 PMCID N/A
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Keywords: Certification, Education, Cardiovascular Magnetic Resonance, Syllabus, Exam
DOI: https://doi.org/10.1093/ehjci/jeu076
Authors: Steffen E Petersen In X Ana G Almeida In X Francisco Alpendurada In X Redha Boubertakh In X Chiara Bucciarelli-Ducci In X Bernard Cosyns In X Gerald F Greil In X Theodoros D Karamitsos In X Patrizio Lancellotti In X Alexandros S Stefanidis In X Oliver Tann In X Mark Westwood In X Sven Plein In X In X
Abstract: An updated version of the European Association of Cardiovascular Imaging (EACVI) Core Syllabus for the European Cardiovascular Magnetic Resonance (CMR) Certification Exam is now available online. The syllabus lists key elements of knowledge in CMR. It represents a framework for the development of training curricula and provides expected knowledge-based learning outcomes to the CMR trainees, in particular those intending to demonstrate CMR knowledge in the European CMR exam, a core requirement in the CMR certification process.
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Reporting standards in cardiac MRI, CT, and SPECT diagnostic accuracy studies: analysis of the impact of STARD criteria.

Issue 6 Vol 15 Published on 2014-06-01 PMID 24459243 PMCID N/A
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Keywords: Diagnostic Accuracy, Stard, Reporting Quality
DOI: https://doi.org/10.1093/ehjci/jet277
Authors: Edd N Maclean In X Ian S Stone In X Felix Ceelen In X Xabier Garcia-Albeniz In X Wieland H Sommer In X Steffen E Petersen In X
Abstract:

Aims

Diagnostic accuracy studies determine the clinical value of non-invasive cardiac imaging tests. The 'STAndards for the Reporting of Diagnostic accuracy studies' (STARD) were published in 2003 to improve the quality of study reporting. We aimed to assess the reporting quality of cardiac computed tomography (CCT), single positron emission computed tomography (SPECT), and cardiac magnetic resonance (CMR) diagnostic accuracy studies; to evaluate the impact of STARD; and to investigate the relationships between reporting quality, journal impact factor, and study citation index.

Methods and results

We randomly generated six groups of 50 diagnostic accuracy studies: 'CMR 1995-2002', 'CMR 2004-11', 'CCT 1995-2002', 'CCT 2004-11', 'SPECT 1995-2002', and 'SPECT 2004-11'. The 300 studies were double-read by two blinded reviewers and reporting quality determined by % adherence to the 25 STARD criteria. Reporting quality increased from 65.3% before STARD to 74.1% after (P = 0.003) in CMR studies and from 61.6 to 79.0% (P < 0.001) in CCT studies. SPECT studies showed no significant change: 71.9% before and 71.5% after STARD (P = 0.92). Journals advising authors to refer to STARD had significantly higher impact factors than those that did not (P = 0.03), and journals with above-median impact factors published studies of significantly higher reporting quality (P < 0.001). Since STARD, citation index has not significantly increased (P = 0.14), but, after adjustment for impact factor, reporting quality continues to increase by ∼1.5% each year.

Conclusion

Reporting standards for diagnostic accuracy studies of non-invasive cardiac imaging are at most satisfactory and have improved since the introduction of STARD. Adherence to STARD should be mandatory for authors of diagnostic accuracy studies.
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An approach for parcellating human cortical areas using resting-state correlations.

Issue N/A Vol 93 Pt 2 Published on 2014-06-01 PMID 23876247 PMCID PMC3912214
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DOI: https://doi.org/10.1016/j.neuroimage.2013.07.035
Authors: Gagan S Wig In X Timothy O Laumann In X Steven E Petersen In X
Abstract: Resting State Functional Connectivity (RSFC) reveals properties related to the brain's underlying organization and function. Features related to RSFC signals, such as the locations where the patterns of RSFC exhibit abrupt transitions, can be used to identify putative boundaries between cortical areas (RSFC-Boundary Mapping). The locations of RSFC-based area boundaries are consistent across independent groups of subjects. RSFC-based parcellation converges with parcellation information from other modalities in many locations, including task-evoked activity and probabilistic estimates of cellular architecture, providing evidence for the ability of RSFC to parcellate brain structures into functionally meaningful units. We not only highlight a collection of these observations, but also point out several limitations and observations that mandate careful consideration in using and interpreting RSFC for the purposes of parcellating the brain's cortical and subcortical structures.
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These abstracts have been selected for presentation in 4 sessions throughout the meeting. Please refer to the PROGRAM for more details.

Issue Suppl 1 Vol 15 Published on 2014-05-01 PMID N/A PMCID PMC4036405
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Authors: K Fischer In X DP Guensch In X N Shie In X MG Friedrich In X G Captur In X F Zemrak In X V Muthurangu In X L Chunming In X SE Petersen In X N Kawel-Boehm In X P Bassett In X PM Elliott In X JAC Lima In X DA Bluemke In X JC Moon In X G Pontone In X E Bertella In X M Loguercio In X A Baggiano In X S Mushtaq In X GD Aquaro In X S Salerni In X C Rossi In X D Andreini In X P Masci In X K Moschetti In X SE Petersen In X G Pilz In X JB Wasserfallen In X M Lombardi In X G Korosoglou In X AC Van Rossum In X O Bruder In X H Mahrholdt In X J Schwitter In X A Florian In X A Ludwig In X S Rösch In X U Sechtem In X A Yilmaz In X A Barison In X NR Pugliese In X PG Masci In X A Del Franco In X G Vergaro In X A Del Torto In X C Passino In X F Perfetto In X M Emdin In X GD Aquaro In X HAI Yoshihara In X JAM Bastiaansen In X C Berthonneche In X A Comment In X J Schwitter In X
Abstract: Background: Altered metabolism is thought to play an important role in the pathogenesis of heart failure. Study of the metabolism may provide insights into the pathology of heart failure and may provide new diagnostic tools. Proton magnetic resonance spectroscopy (MRS) allows us to quantify total creatine, which plays an essential role in the transport of energy from the mitochondria to the myofibrils. Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy. As of yet, proton MRS has not been used to study the changes occurring in this model of heart failure. We aimed to study the metabolic changes occurring in an animal model of EAM, and compare these to the findings in healthy animals. Methods: Myocardial tissue of 10 male young Lewis rats with EAM (35 days after immunization with 0.25 mg porcine myocardial myosine) was analysed using 1H-MAS-MRS (Bruker 600 MHz). The metabolic profile was compared to fresh (n = 7) and frozen (n = 8) healthy controls and to the results from histology and immunohistochemistry (CD68). For fresh control samples the spectra were taken less than 10 min after death. Frozen control samples and myocarditis samples were shock-frozen in liquid nitrogen and stored for 4-6 months at –80°C before measurements. Myocardial tissue from a basal-cavity slice of the the left ventricle (30-40 mg) excluding epicardial tissue was placed in a 4 mm zirconium rotor, packed homogeneously using a spacer and spun at 4 kHz at 293 K. A water suppression pulse sequence was applied to obtain the proton spectrum (ns = 128, t = 7 min). Spectra were phased and baseline correction using polynomial fit to the region of interest was applied before integration of the peaks. Results: The metabolic ratio of taurine to creatine obtained by spectral analysis proved to be a significant biomarker for diagnosis of myocarditis compared to healthy controls (taurine/creatine ratio in myocarditis: 4.47(±0.83), fresh control: 2.59(±0.09), frozen control: 2.59(±0.28); P < 0.001). Myocarditis was confirmed histologically with an inflammatory cellular infiltrate and CD68 positive staining. Conclusions: Myocardial taurine/creatine ratio as detected by proton MRS is able to differentiate between healthy myocardium and myocardium from rats with EAM. This variation may occur due to creatine depletion as described in heart failure and/or an increase in taurine due to its antioxidant activity in inflammatory reactions. Objectives: The relationship between the severity of coronary stenosis and the severity of stress perfusion abnormalities was important in the validation of quantitative Positron Emission Tomography stress perfusion. We studied myocardial blood flow (MBF) derived from regadenoson stress Cardiac MRI (CMR) quantified to the pixel level in units of ml/min/g and compared results with quantitative coronary angiography (QCA) at the vessel level. Methods: Regadenoson perfusion CMR (steady state free precession and 0.05 mmol/kg gadolinium) was quantified at the pixel level with model-constrained Fermi deconvolution. QCA was available in 51 subjects after excluding patients with coronary artery bypass, congenital disease, hypertrophic cardiomyopathy, and catheterization technical issues. Five subjects were excluded for CMR technical issues. Regions of interest were drawn in the three layers of the myocardium. Endocardial/epicardial MBF ratio was defined as endocardial MBF/(average epicardial MBF in that coronary distribution). Results: The 46 patients in this study averaged 61.3 ± 10.8 years, 61% were male, and 35% had prior percutaneous coronary intervention. At a QCA threshold of 50%, the Left Anterior Descending was abnormal in 32, Right Coronary Artery in 24, Circumflex in 18, and leaving 63 coronary arteries with 0-49% stenosis. Stress endocardial MBF averaged 2.28 ml/min/g in normal segments which was higher than in segments with ≥50% QCA stenosis (1.24 ml/min/g; p < 0.0001). There was a graded severity in stress endocardial/epicardial MBF ratio vs severity of QCA stenosis (Figure). In receiver operating characteristics curve analysis, endocardial/epicardial MBF discriminated ≥50% QCA stenosis from normal (area under the curve (AUC) 0.949, p < 0.001); absolute endocardial MBF had an AUC of 0.903 (p < 0.001) and myocardial perfusion reserve had an AUC of 0.881 (p < 0.001). Conclusions: Myocardial perfusion quantified at the pixel level detects significant coronary artery disease at the coronary vessel level objectively and with high diagnostic discrimination from normal.
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EuroEcho-Imaging 2013: highlights.

Issue 5 Vol 15 Published on 2014-05-01 PMID 24569182 PMCID N/A
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Keywords: Heart Failure, Heart valve diseases, Nuclear Cardiology, Cardiac Computed Tomography, Cardiovascular Magnetic Resonance, Congenital Heart Diseases, 3d Echocardiography
DOI: https://doi.org/10.1093/ehjci/jeu021
Authors: Patrizio Lancellotti In X Julien Magne In X Bernard Cosyns In X Erwan Donal In X Anastasia Kitsiou In X Owen Miller In X Steffen E Petersen In X Gilbert Habib In X
Abstract: The annual meeting of the European Association of Echocardiography (EuroEcho-Imaging) was held in Istanbul, Turkey. In the present paper, we present a summary of the 'Highlights' session.
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Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high-motion data points.

Issue 5 Vol 35 Published on 2014-05-01 PMID 23861343 PMCID PMC3895106
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Keywords: Noise, fMRI, Motion, Data Quality, GLM, Task, General Linear Model, Head Movement, Scrubbing
DOI: https://doi.org/10.1002/hbm.22307
Authors: Joshua S Siegel In X Jonathan D Power In X Joseph W Dubis In X Alecia C Vogel In X Jessica A Church In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Subject motion degrades the quality of task functional magnetic resonance imaging (fMRI) data. Here, we test two classes of methods to counteract the effects of motion in task fMRI data: (1) a variety of motion regressions and (2) motion censoring ("motion scrubbing"). In motion regression, various regressors based on realignment estimates were included as nuisance regressors in general linear model (GLM) estimation. In motion censoring, volumes in which head motion exceeded a threshold were withheld from GLM estimation. The effects of each method were explored in several task fMRI data sets and compared using indicators of data quality and signal-to-noise ratio. Motion censoring decreased variance in parameter estimates within- and across-subjects, reduced residual error in GLM estimation, and increased the magnitude of statistical effects. Motion censoring performed better than all forms of motion regression and also performed well across a variety of parameter spaces, in GLMs with assumed or unassumed response shapes. We conclude that motion censoring improves the quality of task fMRI data and can be a valuable processing step in studies involving populations with even mild amounts of head movement.
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Development and validation of a scoring system for late anorectal side-effects in patients treated with radiotherapy for prostate cancer.

Issue 1 Vol 111 Published on 2014-04-01 PMID 24630536 PMCID N/A
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Keywords: Radiotherapy, Quality of life, prostate cancer, Late Morbidity
DOI: https://doi.org/10.1016/j.radonc.2014.01.023
Authors: Stine Elleberg Petersen In X Lise Bentzen In X Katrine J Emmertsen In X Søren Laurberg In X Lilli Lundby In X Morten Høyer In X
Abstract:

Purpose

To develop and validate a scoring system for evaluation of long term anorectal dysfunction following radiotherapy for prostate cancer.

Materials and methods

Patients treated for prostate cancer with radiotherapy filled in questionnaires on anorectal function and quality of life. Items for the condensed anorectal dysfunction score (RT-ARD) were identified and weighted by binomial regression analysis. The score was tested in a separate patient material by receiver operating characteristic (ROC) analysis and correlations to quality of life domains.

Results

A total of 309 patients participated in the study. The items selected were "incontinence for solid stool", "ability to defer defecation", "unproductive call to stool", "clustering of stool", and "mucus in stool." Patients were grouped into three categories according to the RT-ARD score; 0-8 (no RT-ARD), 9-23 (minor RT-ARD), 24-45 (major RT-ARD). ROC analyses revealed high sensitivity (91%) and specificity (85%) for major RT-ARD. The prediction model demonstrated a perfect fit in 60%, moderate fit in 36% and no fit in 4%. There was good correlation between the RT-ARD score and quality of life.

Conclusions

The RT-ARD score is a validated and simple instrument for evaluation of anorectal dysfunction following radiotherapy for prostate cancer, and the RT-ARD score correlates to the patient's quality of life.
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Interactions between concentric form-from-structure and face perception revealed by visual masking but not adaptation.

Issue 2 Vol 14 Published on 2014-02-01 PMID 24563526 PMCID PMC3934487
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Keywords: Visual Masking, Face Perception, Holistic Processing, Visual Adaptation, Glass Patterns, Moire Perception
DOI: https://doi.org/10.1167/14.2.15
Authors: Eric Feczko In X Gordon L Shulman In X Steven E Petersen In X John R Pruett In X
Abstract: Findings from diverse subfields of vision research suggest a potential link between high-level aspects of face perception and concentric form-from-structure perception. To explore this relationship, typical adults performed two adaptation experiments and two masking experiments to test whether concentric, but not nonconcentric, Glass patterns (a type of form-from-structure stimulus) utilize a processing mechanism shared by face perception. For the adaptation experiments, subjects were presented with an adaptor for 5 or 20 s, prior to discriminating a target. In the masking experiments, subjects saw a mask, then a target, and then a second mask. Measures of discriminability and bias were derived and repeated measures analysis of variance tested for pattern-specific masking and adaptation effects. Results from Experiment 1 show no Glass pattern-specific effect of adaptation to faces; results from Experiment 2 show concentric Glass pattern masking, but not adaptation, may impair upright/inverted face discrimination; results from Experiment 3 show concentric and radial Glass pattern masking impaired subsequent upright/inverted face discrimination more than translational Glass pattern masking; and results from Experiment 4 show concentric and radial Glass pattern masking impaired subsequent face gender discrimination more than translational Glass pattern masking. Taken together, these findings demonstrate interactions between concentric form-from-structure and face processing, suggesting a possible common processing pathway.
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Diagnostic performance and comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic overview.

Issue 10 Vol 16 Published on 2014-01-01 PMID 25301401 PMCID N/A
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DOI: https://doi.org/10.1007/s11886-014-0537-9
Authors: Claudia N van Waardhuizen In X Marieke Langhout In X Felisia Ly In X Loes Braun In X Tessa S S Genders In X Steffen E Petersen In X Kirsten E Fleischmann In X Koen Nieman In X M G Myriam Hunink In X
Abstract: Several non-invasive imaging techniques are currently in use for the diagnostic workup of adult patients with stable chest pain suspected of having coronary artery disease (CAD). In this paper, we present a systematic overview of the evidence on diagnostic performance and comparative cost-effectiveness of new modalities in comparison to established technologies. A literature search for English language studies from 2009 to 2013 was performed, and two investigators independently extracted data on patient and study characteristics. The reviewed published evidence on diagnostic performance and cost-effectiveness support a strategy of CTCA as a rule out (gatekeeper) test of CAD in low- to intermediate-risk patients since it has excellent diagnostic performance and as initial imaging test is cost-effective under different willingness-to-pay thresholds. More cost-effectiveness research is needed in order to define the role and choice of cardiac stress imaging tests.
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The VWFA: it's not just for words anymore.

Open Access Issue N/A Vol 8 Published on 2014-01-01 PMID 24688462 PMCID PMC3960495
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Keywords: fMRI, Reading, Orthography, Resting-state Fmri, Resting-state Networks, Resting-state Functional Connectivity, Visual Word Form Area, Occipito-temporal Cortex
DOI: https://doi.org/10.3389/fnhum.2014.00088
Authors: Alecia C Vogel In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Reading is an important but phylogenetically new skill. While neuroimaging studies have identified brain regions used in reading, it is unclear to what extent these regions become specialized for use predominantly in reading vs. other tasks. Over the past several years, our group has published three studies addressing this question, particularly focusing on whether the putative visual word form area (VWFA) is used predominantly in reading, or whether it is used more generally in a number of tasks. Our three studies utilize a range of neuroimaging techniques, including task based fMRI experiments, a seed based resting state functional connectivity (RSFC) experiment, and a network based RSFC experiment. Overall, our studies indicate that the VWFA is not used specifically or even predominantly for reading. Rather the VWFA is a general use region that has processing properties making it particularly useful for reading, though it continues to be used in any task that requires its general processing properties. Our network based RSFC analysis extends this finding to other regions typically thought to be used predominantly for reading. Here, we review these findings and describe how the three studies complement each other. Then, we argue that conceptualizing the VWFA as a brain region with specific processing characteristics rather than a brain region devoted to a specific stimulus class, allows us to better explain the activity seen in this region during a variety of tasks. Having this type of conceptualization not only provides a better understanding of the VWFA but also provides a framework for understanding other brain regions, as it affords an explanation of function that is in keeping with the long history of studying the brain in terms of the type of information processing performed (Posner, 1978).
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Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.

Open Access Issue N/A Vol 16 Published on 2014-01-01 PMID 24461028 PMCID PMC4015639
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DOI: https://doi.org/10.1186/1532-429x-16-13
Authors: Karine Moschetti In X David Favre In X Christophe Pinget In X Guenter Pilz In X Steffen E Petersen In X Anja Wagner In X Jean-Blaise Wasserfallen In X Juerg J Schwitter In X
Abstract:

Background

According to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared.

Methods

Strategy 1) CMR to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA), Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA + FFR). The costs, evaluated from the third party payer perspective in Switzerland, Germany, the United Kingdom (UK), and the United States (US), included public prices of the different outpatient procedures and costs induced by procedural complications and by diagnostic errors. The effectiveness criterion was the correct identification of hemodynamically significant coronary lesion(s) (= significant CAD) complemented by full anatomical information. Test performances were derived from the published literature. Cost-effectiveness ratios for both strategies were compared for hypothetical cohorts with different pretest likelihood of significant CAD.

Results

CMR + CXA and CXA + FFR were equally cost-effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany, 83% in the UK, and 82% in the US with costs of CHF 5'794, € 1'517, £ 2'680, and $ 2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR.

Conclusions

The CMR + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of 62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care systems, respectively. These findings may help to optimize resource utilization in the diagnosis of CAD.
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Quantitative computed tomographic coronary angiography: does it predict functionally significant coronary stenoses?

Issue 1 Vol 7 Published on 2014-01-01 PMID 24280729 PMCID N/A
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Keywords: Coronary stenosis, Ct Coronary Angiography, Fractional Flow Reserve
DOI: https://doi.org/10.1161/circimaging.112.000277
Authors: Alexia Rossi In X Stella-Lida Papadopoulou In X Francesca Pugliese In X Brunella Russo In X Anoeshka S Dharampal In X Admir Dedic In X Pieter H Kitslaar In X Alexander Broersen In X W Bob Meijboom In X Robert-Jan van Geuns In X Andrew Wragg In X Jurgen Ligthart In X Carl Schultz In X Steffen E Petersen In X Koen Nieman In X Gabriel P Krestin In X Pim J de Feyter In X
Abstract:

Background

Coronary lesions with a diameter narrowing ≥50% on visual computed tomographic coronary angiography (CTCA) are generally considered for referral to invasive coronary angiography. However, similar to invasive coronary angiography, visual CTCA is often inaccurate in detecting functionally significant coronary lesions. We sought to compare the diagnostic performance of quantitative CTCA with visual CTCA for the detection of functionally significant coronary lesions using fractional flow reserve (FFR) as the reference standard.

Methods and results

CTCA and FFR measurements were obtained in 99 symptomatic patients. In total, 144 coronary lesions detected on CTCA were visually graded for stenosis severity. Quantitative CTCA measurements included lesion length, minimal area diameter, % area stenosis, minimal lumen diameter, % diameter stenosis, and plaque burden [(vessel area-lumen area)/vessel area×100]. Optimal cutoff values of CTCA-derived parameters were determined, and their diagnostic accuracy for the detection of flow-limiting coronary lesions (FFR≤0.80) was compared with visual CTCA. FFR was ≤0.80 in 54 of 144 (38%) coronary lesions. Optimal cutoff values to predict flow-limiting coronary lesion were 10 mm for lesion length, 1.8 mm2 for minimal area diameter, 73% for % area stenosis, 1.5 mm for minimal lumen diameter, 48% for % diameter stenosis, and 76% for plaque burden. No significant difference in sensitivity was found between visual CTCA and quantitative CTCA parameters (P>0.05). The specificity of visual CTCA (42%; 95% confidence interval [CI], 31%-54%) was lower than that of minimal area diameter (68%; 95% CI, 57%-77%; P=0.001), % area stenosis (76%; 95% CI, 65%-84%; P<0.001), minimal lumen diameter (67%; 95% CI, 55%-76%; P=0.001), % diameter stenosis (72%; 95% CI, 62%-80%; P<0.001), and plaque burden (63%; 95% CI, 52%-73%; P=0.004). The specificity of lesion length was comparable with that of visual CTCA.

Conclusions

Quantitative CTCA improves the prediction of functionally significant coronary lesions compared with visual CTCA assessment but remains insufficient. Functional assessment is still required in lesions of moderate stenosis to accurately detect impaired FFR.
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Methods to detect, characterize, and remove motion artifact in resting state fMRI.

Issue N/A Vol 84 Published on 2014-01-01 PMID 23994314 PMCID PMC3849338
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Keywords: Movement, MRI, Motion, Resting state, Functional Connectivity, Artifact
DOI: https://doi.org/10.1016/j.neuroimage.2013.08.048
Authors: Jonathan D Power In X Anish Mitra In X Timothy O Laumann In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Head motion systematically alters correlations in resting state functional connectivity fMRI (RSFC). In this report we examine impact of motion on signal intensity and RSFC correlations. We find that motion-induced signal changes (1) are often complex and variable waveforms, (2) are often shared across nearly all brain voxels, and (3) often persist more than 10s after motion ceases. These signal changes, both during and after motion, increase observed RSFC correlations in a distance-dependent manner. Motion-related signal changes are not removed by a variety of motion-based regressors, but are effectively reduced by global signal regression. We link several measures of data quality to motion, changes in signal intensity, and changes in RSFC correlations. We demonstrate that improvements in data quality measures during processing may represent cosmetic improvements rather than true correction of the data. We demonstrate a within-subject, censoring-based artifact removal strategy based on volume censoring that reduces group differences due to motion to chance levels. We note conditions under which group-level regressions do and do not correct motion-related effects.
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Diagnostic performance of hyperaemic myocardial blood flow index obtained by dynamic computed tomography: does it predict functionally significant coronary lesions?

Issue 1 Vol 15 Published on 2014-01-01 PMID 23935153 PMCID N/A
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Keywords: Myocardial perfusion, Myocardial blood flow, coronary artery disease, Coronary Computed Tomography Angiography, Dynamic Contrast-enhanced Computed Tomography
DOI: https://doi.org/10.1093/ehjci/jet133
Authors: Alexia Rossi In X Anoeshka Dharampal In X Andrew Wragg In X L Ceri Davies In X Robert Jan van Geuns In X Costantinos Anagnostopoulos In X Ernst Klotz In X Pieter Kitslaar In X Alexander Broersen In X Anthony Mathur In X Koen Nieman In X M G Myriam Hunink In X Pim J de Feyter In X Steffen E Petersen In X Francesca Pugliese In X
Abstract:

Aims

The severity of coronary artery narrowing is a poor predictor of functional significance, in particular in intermediate coronary lesions (30-70% diameter narrowing). The aim of this work was to compare the performance of a quantitative hyperaemic myocardial blood flow (MBF) index derived from adenosine dynamic computed tomography perfusion (CTP) imaging with that of visual CT coronary angiography (CTCA) and semi-automatic quantitative CT (QCT) in the detection of functionally significant coronary lesions in patients with stable chest pain.

Methods and results

CTCA and CTP were performed in 80 patients (210 analysable coronary vessels) referred to invasive coronary angiography (ICA). The MBF index (mL/100 mL/min) was computed using a model-based parametric deconvolution method. The diagnostic performance of the MBF index in detecting functionally significant coronary lesions was compared with visual CTCA and QCT. Coronary lesions with invasive fractional flow reserve of ≤0.75 were defined as functionally significant. The optimal cut-off value of the MBF index to detect functionally significant coronary lesions was 78 mL/100 mL/min. On a vessel-territory level, the MBF index had a larger area under the curve (0.95; 95% confidence interval [95% CI]: 0.92-0.98) compared with visual CTCA (0.85; 95% CI: 0.79-0.91) and QCT (0.89; 95% CI: 0.84-0.93) (both P-values <0.001). In the analysis restricted to intermediate coronary lesions, the specificity of visual CTCA (69%) and QCT (77%) could be improved by the subsequent use of the MBF index (89%).

Conclusion

In this proof-of-principle study, the MBF index performed better than visual CTCA and QCT in the identification of functionally significant coronary lesions. The MBF index had additional value beyond CTCA anatomy in intermediate coronary lesions. This may have a potential to support patient management.
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Effect of atrial fibrillation ablation on myocardial function: insights from cardiac magnetic resonance feature tracking analysis.

Issue 8 Vol 29 Published on 2013-12-01 PMID 24002783 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1007/s10554-013-0287-6
Authors: Felix Ceelen In X Ross J Hunter In X Redha Boubertakh In X Wieland H Sommer In X Marco Armbruster In X Richard J Schilling In X Steffen E Petersen In X
Abstract: Restoration of sinus rhythm may result in an improvement of left heart function in patients with atrial fibrillation (AF). Cardiovascular magnetic resonance (CMR) feature tracking (FT) technique may help detect subtle wall-motion abnormalities. Consequently this study aimed to analyse existence and reversibility of subclinical cardiac dysfunction following atrial fibrillation ablation. 28 consecutive patients (mean age 61 years) with paroxysmal AF underwent pulmonary vein isolation. CMR imaging was done 3 (±3) days before and 3.4 (±1.1) months after ablation. Left heart function was determined by performing FT analysis. Statistical analysis included paired student's t test, random effects metaanalysis to assess the cohort's health status and Bland-Altman analysis. 17 patients (61%) were free from AF at follow-up. Bland-Altman analysis showed good coefficients of variation. Of all 195 parameters, 27 changed (14%): 9 improved significantly (5%), 12 worsened significantly (6%), whereas 6 parameters worsened not significantly (3%). 18 of 120 systolic parameters changed (15%), 14 worsened (12%), 4 improved (3%). In 9 of 75 diastolic parameters, values changed (12%): 5 improved (7%) and 4 worsened (5%). Meta-analysis revealed that our collective's FT values at baseline didn't differ significantly from healthy volunteers' values [Q values of 0.01 (p value 0.921) and 1.499 (p value 0.221)]. AF patients undergoing ablation appear to have near normal cardiac wall motion, which does not improve following successful ablation. Feature tracking analysis is a reliable tool to determine treatment effects but is more likely to show positive findings if the population is unhealthy.
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The critical roles of localization and physiology for understanding parietal contributions to memory retrieval.

Issue 6 Vol 19 Published on 2013-12-01 PMID 23778789 PMCID N/A
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Keywords: fMRI, Parietal cortex, Memory Retrieval, Functional Connectivity, Parcellation, Baseline
DOI: https://doi.org/10.1177/1073858413492389
Authors: Steven M Nelson In X Kathleen B McDermott In X Gagan S Wig In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Functional magnetic resonance imaging (fMRI) studies of recognition memory ubiquitously demonstrate retrieval-related activity in left lateral parietal cortex (LLPC) when contrasting studied ("old") items with unstudied ("new") items. Recent work demonstrates that there is considerable functional-anatomical heterogeneity in LLPC. One implication of this observation is that single- or dual-process models fall short of characterizing LLPC contributions to memory retrieval. Instead of considering LLPC as a single entity, functional accounts must be given for each of the distinct regions that show retrieval-related effects; we posit there are a minimum of four such regions and very likely more. Identification of these LLPC regions requires careful analysis to map the boundaries and the extent of the regions precisely. In addition, characterizing the functional responses as activations or deactivations relative to baseline will be crucial in understanding the underlying cognitive processes. Considering LLPC in both memory and "nonmemory" domains will also illuminate the contribution of these regions, because it is certainly unlikely they serve only the domain of memory retrieval.
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Reproducibility of arterial stiffness and wave reflections in chronic obstructive pulmonary disease: the contribution of lung hyperinflation and a comparison of techniques.

Issue 11 Vol 107 Published on 2013-11-01 PMID 23920329 PMCID N/A
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Keywords: Pulse wave velocity, Cardiovascular disease, Augmentation Index, Copd Co-morbidities, Sphygmocor, Vicorder
DOI: https://doi.org/10.1016/j.rmed.2013.06.008
Authors: Ian S Stone In X Leonette John In X Steffen E Petersen In X Neil C Barnes In X
Abstract: Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease (COPD). Arterial stiffness is raised in COPD and may be a mechanistic link. Non-invasive assessment of arterial stiffness has the potential to be a surrogate outcome measure, although no reproducibility data exists in COPD patients. Two studies (23 and 33 COPD patients) were undertaken to 1) assess the Vicorder reproducibility of carotid-femoral pulse wave velocity and Augmentation index in COPD; 2) compare it to SphygmoCor; and 3) assess the contribution of lung hyperinflation to measurement variability. There were excellent correlations and good agreement between repeat Vicorder measurements for carotid-femoral pulse wave velocity (r = 0.96 (p < 0.001); mean difference ±SD = -0.03 ± 0.36 m/s (p = 0.65); co-efficient of reproducibility = 4.02%; limits of agreement = -0.68-0.75 m/s). Augmentation index significantly correlated (r = 0.736 (p < 0.001); mean difference ±SD = 0.72 ± 4.86% (p = 0.48), however limits of agreement were only 10.42-9.02%, with co-efficient of reproducibility of 27.93%. Comparing devices, Vicorder values were lower but there was satisfactory agreement. There were no correlation between lung hyperinflation (as measured by residual volume percent predicted, total lung capacity percent predicted or the ratio of inspiratory capacity to residual volume) and variability of measurements in either study. In COPD, measurement of carotid-femoral pulse wave velocity is highly reproducible, not affected by lung hyperinflation and suitable as a surrogate endpoint in research studies. Day-to-day variation in augmentation index highlights the importance of such studies prior to the planning and undertaking of clinical COPD research.
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Function in the human connectome: task-fMRI and individual differences in behavior.

Issue N/A Vol 80 Published on 2013-10-01 PMID 23684877 PMCID PMC4011498
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Keywords: Connectivity, Personality, emotion, Individual Differences, Cognitive, Sensory And Motor Function, Task-fmri
DOI: https://doi.org/10.1016/j.neuroimage.2013.05.033
Authors: Deanna M Barch In X Gregory C Burgess In X Michael P Harms In X Steven E Petersen In X Bradley L Schlaggar In X Maurizio Corbetta In X Matthew F Glasser In X Sandra Curtiss In X Sachin Dixit In X Cindy Feldt In X Dan Nolan In X Edward Bryant In X Tucker Hartley In X Owen Footer In X James M Bjork In X Russ Poldrack In X Steve Smith In X Heidi Johansen-Berg In X Abraham Z Snyder In X David C Van Essen In X In X
Abstract: The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels.
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Matching is not naming: a direct comparison of lexical manipulations in explicit and implicit reading tasks.

Issue 10 Vol 34 Published on 2013-10-01 PMID 22711620 PMCID PMC4176923
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Keywords: Adult, fMRI, Language, Phonology, Orthography, Spoken
DOI: https://doi.org/10.1002/hbm.22077
Authors: Alecia C Vogel In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The neurobiological basis of reading is of considerable interest, yet analyzing data from subjects reading words aloud during functional MRI data collection can be difficult. Therefore, many investigators use surrogate tasks such as visual matching or rhyme matching to eliminate the need for spoken output. Use of these tasks has been justified by the presumption of "automatic activation" of reading-related neural processing when a word is viewed. We have tested the efficacy of using a nonreading task for studying "reading effects" by directly comparing blood oxygen level dependent (BOLD) activity in subjects performing a visual matching task and an item naming task on words, pseudowords (meaningless but legal letter combinations), and nonwords (meaningless and illegal letter combinations). When compared directly, there is significantly more activity during the naming task in "reading-related" regions such as the inferior frontal gyrus (IFG) and supramarginal gyrus. More importantly, there are differing effects of lexicality in the tasks. A whole-brain task (matching vs. naming) by string type (word vs. pseudoword vs. nonword) by BOLD timecourse analysis identifies regions showing this three-way interaction, including the left IFG and left angular gyrus (AG). In the majority of the identified regions (including the left IFG and left AG), there is a string type × timecourse interaction in the naming but not the matching task. These results argue that the processing performed in specific regions is contingent on task, even in reading-related regions and is thus nonautomatic. Such differences should be taken into consideration when designing studies intended to investigate reading.
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CMR and LV noncompaction: does it matter how we measure trabeculations?

Issue 9 Vol 6 Published on 2013-09-01 PMID 24029367 PMCID N/A
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Keywords: Prognosis, Bayes, Pre-test Probability, Post-test Probability, Diagnostic Accuracy, Cardiovascular Magnetic Resonance, Cmr, Left Ventricular Noncompaction, Lvnc
DOI: https://doi.org/10.1016/j.jcmg.2013.03.007
Authors: Steffen E Petersen In X
Abstract: No Abstract Available
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Concentric left ventricular remodeling and aortic stiffness: a comparison of obesity and hypertension.

Issue 6 Vol 167 Published on 2013-09-01 PMID 23041005 PMCID N/A
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Keywords: Hypertension, Obesity, Left ventricular hypertrophy, Magnetic Resonance Imaging, Aortic Stiffness
DOI: https://doi.org/10.1016/j.ijcard.2012.08.049
Authors: Oliver J Rider In X Richard Nethononda In X Steffen E Petersen In X Jane M Francis In X James P Byrne In X Paul Leeson In X Kieran Clarke In X Stefan Neubauer In X
Abstract:

Background

Increased thoracic ascending aortic stiffness is thought to contribute to concentric left ventricular hypertrophy and increased mortality, a pattern seen in hypertension. As such, aortic stiffness and increased left ventricular mass are candidates by which obesity increases cardiovascular risk. However, obesity is characterized predominantly by increased abdominal aortic stiffness and with eccentric left ventricular hypertrophy.

Methods

We aimed to establish whether or not, in addition to these changes, there is also an element of concentric remodeling in obesity that was predicted by ascending aortic stiffness. 301 subjects underwent cardiovascular magnetic resonance imaging to measure regional aortic distensibility and left ventricular morphology. To compare obesity with hypertension, subjects were separated into groups by hypertensive status and body mass index.

Results

In comparison to normotensive subjects, hypertension was linked with concentric remodeling (a 17% increase in left ventricular mass:volume ratio (LVM:VR), (p<0.001)) and reduced ascending aortic distensibility (by 64%,p<0.001). LVM:VR was negatively correlated with ascending aortic distensibility (R=-0.36,p<0.01). Obesity, in the absence of hypertension, was associated with elevated left ventricular mass when compared to normal weight normotensive subjects (by 27%, p<0.01), in an eccentric pattern with cavity dilatation (p<0.01). However, LVM:VR was also 14% larger than in normal weight normotensive subjects (p<0.01), indicative of additional concentric remodeling. LVM:VR in obesity was, however, not correlated with ascending aortic distensibility when adjusted for mean arterial pressure (R=-0.14,p<0.14).

Conclusion

In summary, despite the predominantly eccentric pattern of left hypertrophy in obesity there is a concentric element of hypertrophy that, unlike in hypertension, is not linked to increased ascending aortic stiffness.
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Evidence for hubs in human functional brain networks.

Issue 4 Vol 79 Published on 2013-08-01 PMID 23972601 PMCID PMC3838673
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DOI: https://doi.org/10.1016/j.neuron.2013.07.035
Authors: Jonathan D Power In X Bradley L Schlaggar In X Christina N Lessov-Schlaggar In X Steven E Petersen In X
Abstract: Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting-state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: (1) finding network nodes that participate in multiple subnetworks of the brain, and (2) finding spatial locations in which several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity.
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Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: a 2-center study.

Open Access Issue 8 Vol 10 Published on 2013-08-01 PMID 23685170 PMCID PMC3734347
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Keywords: Electrocardiogram, PAF, Atrial fibrillation, Magnetic resonance angiography, SD, MRA, LA, ECG, Radiofrequency, Paroxysmal atrial fibrillation, RF, Radiofrequency Ablation, Standard Deviation, Cardiovascular Magnetic Resonance, Cmr, 2d, Af, Late Gadolinium Enhancement, Lge, 2-Dimensional, Delayed-enhancement Magnetic Resonance Imaging, Left Atrial/atrium
DOI: https://doi.org/10.1016/j.hrthm.2013.04.030
Authors: L C Malcolme-Lawes In X C Juli In X R Karim In X W Bai In X R Quest In X P B Lim In X S Jamil-Copley In X P Kojodjojo In X B Ariff In X D W Davies In X D Rueckert In X D P Francis In X R Hunter In X D Jones In X R Boubertakh In X S E Petersen In X R Schilling In X P Kanagaratnam In X N S Peters In X
Abstract:

Background

For late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) assessment of atrial scar to guide management and targeting of ablation in atrial fibrillation (AF), an objective, reproducible method of identifying atrial scar is required.

Objective

To describe an automated method for operator-independent quantification of LGE that correlates with colocated endocardial voltage and clinical outcomes.

Methods

LGE CMR imaging was performed at 2 centers, before and 3 months after pulmonary vein isolation for paroxysmal AF (n = 50). A left atrial (LA) surface scar map was constructed by using automated software, expressing intensity as multiples of standard deviation (SD) above blood pool mean. Twenty-one patients underwent endocardial voltage mapping at the time of pulmonary vein isolation (11 were redo procedures). Scar maps and voltage maps were spatially registered to the same magnetic resonance angiography (MRA) segmentation.

Results

The LGE levels of 3, 4, and 5SDs above blood pool mean were associated with progressively lower bipolar voltages compared to the preceding enhancement level (0.85 ± 0.33, 0.50 ± 0.22, and 0.38 ± 0.28 mV; P = .002, P < .001, and P = .048, respectively). The proportion of atrial surface area classified as scar (ie, >3 SD above blood pool mean) on preablation scans was greater in patients with postablation AF recurrence than those without recurrence (6.6% ± 6.7% vs 3.5% ± 3.0%, P = .032). The LA volume >102 mL was associated with a significantly greater proportion of LA scar (6.4% ± 5.9% vs 3.4% ± 2.2%; P = .007).

Conclusions

LA scar quantified automatically by a simple objective method correlates with colocated endocardial voltage. Greater preablation scar is associated with LA dilatation and AF recurrence.
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Steps toward optimizing motion artifact removal in functional connectivity MRI; a reply to Carp.

Issue N/A Vol 76 Published on 2013-08-01 PMID 22440651 PMCID PMC3834590
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Keywords:
DOI: https://doi.org/10.1016/j.neuroimage.2012.03.017
Authors: Jonathan D Power In X Kelly Anne Barnes In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: No Abstract Available
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Use of cardiac magnetic resonance and echocardiography in population-based studies: why, where, and when?

Issue 4 Vol 6 Published on 2013-07-01 PMID 23861451 PMCID N/A
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Keywords: Population, Echocardiography, epidemiology, Magnetic Resonance Imaging, Cardiac Magnetic Resonance
DOI: https://doi.org/10.1161/circimaging.113.000498
Authors: Thomas H Marwick In X Stefan Neubauer In X Steffen E Petersen In X
Abstract: No Abstract Available
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Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches.

Open Access Issue N/A Vol 15 Published on 2013-05-01 PMID 23714095 PMCID PMC3668194
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Keywords:
DOI: https://doi.org/10.1186/1532-429x-15-46
Authors: Steffen E Petersen In X Paul M Matthews In X Fabian Bamberg In X David A Bluemke In X Jane M Francis In X Matthias G Friedrich In X Paul Leeson In X Eike Nagel In X Sven Plein In X Frank E Rademakers In X Alistair A Young In X Steve Garratt In X Tim Peakman In X Jonathan Sellors In X Rory Collins In X Stefan Neubauer In X
Abstract: UK Biobank is a prospective cohort study with 500,000 participants aged 40 to 69. Recently an enhanced imaging study received funding. Cardiovascular magnetic resonance (CMR) will be part of a multi-organ, multi-modality imaging visit in 3-4 dedicated UK Biobank imaging centres that will acquire and store imaging data from 100,000 participants (subject to successful piloting). In each of UK Biobank's dedicated bespoke imaging centres, it is proposed that 15-20 participants will undergo a 2 to 3 hour visit per day, seven days a week over a period of 5-6 years. The imaging modalities will include brain MRI at 3 Tesla, CMR and abdominal MRI at 1.5 Tesla, carotid ultrasound and DEXA scans using carefully selected protocols. We reviewed the rationale, challenges and proposed approaches for concise phenotyping using CMR on such a large scale. Here, we discuss the benefits of this imaging study and review existing and planned population based cardiovascular imaging in prospective cohort studies. We will evaluate the CMR protocol, feasibility, process optimisation and costs. Procedures for incidental findings, quality control and data processing and analysis are also presented. As is the case for all other data in the UK Biobank resource, this database of images and related information will be made available through UK Biobank's Access Procedures to researchers (irrespective of their country of origin and whether they are academic or commercial) for health-related research that is in the public interest.
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Functional network architecture of reading-related regions across development.

Issue 2 Vol 125 Published on 2013-05-01 PMID 23506969 PMCID PMC3863779
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Keywords:
DOI: https://doi.org/10.1016/j.bandl.2012.12.016
Authors: Alecia C Vogel In X Jessica A Church In X Jonathan D Power In X Fran M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Reading requires coordinated neural processing across a large number of brain regions. Studying relationships between reading-related regions informs the specificity of information processing performed in each region. Here, regions of interest were defined from a meta-analysis of reading studies, including a developmental study. Relationships between regions were defined as temporal correlations in spontaneous fMRI signal; i.e., resting state functional connectivity MRI (RSFC). Graph theory based network analysis defined the community structure of the "reading-related" regions. Regions sorted into previously defined communities, such as the fronto-parietal and cingulo-opercular control networks, and the default mode network. This structure was similar in children, and no apparent "reading" community was defined in any age group. These results argue against regions, or sets of regions, being specific or preferential for reading, instead indicating that regions used in reading are also used in a number of other tasks.
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Control-related systems in the human brain.

Issue 2 Vol 23 Published on 2013-04-01 PMID 23347645 PMCID PMC3632325
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Keywords:
DOI: https://doi.org/10.1016/j.conb.2012.12.009
Authors: Jonathan D Power In X Steven E Petersen In X
Abstract: A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control.
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Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience.

Issue 4 Vol 24 Published on 2013-04-01 PMID 23293924 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1111/jce.12063
Authors: Ross J Hunter In X Daniel A Jones In X Redha Boubertakh In X Louisa C Malcolme-Lawes In X Prapa Kanagaratnam In X Christoph F Juli In X D Wyn Davies In X Nicholas S Peters In X Victoria Baker In X Mark J Earley In X Simon Sporton In X L Ceri Davies In X Mark Westwood In X Steffen E Petersen In X Richard J Schilling In X
Abstract:

Introduction

We tested the hypothesis that cardiovascular magnetic resonance (CMR) imaging can reliably distinguish the presence or absence of left atrial (LA) ablation lesions by blinded analysis of pre- and postablation imaging.

Methods

Consecutive patients at 2 centers undergoing pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation by either wide area circumferential radiofrequency ablation (WACA) or ostial ablation with a cryoballoon underwent CMR late gadolinium enhancement (LGE) imaging pre- and 3 months postablation. Imaging was anonymized for blinded analysis of (1) LGE images, and (2) a 3D fusion image with LGE projected onto a segmented LA surface. Scans were categorized using both assessment techniques separately as pre- or postablation, and if postablation, whether lesions were in an ostial or WACA distribution.

Results

LGE imaging was performed in 50 patients (aged 60 ± 10 years, 68% male, 24 underwent WACA and 26 had cryoablation). Sensitivity and specificity for detection of ablation lesions was 60% and 96% on LGE imaging. Sensitivity was higher using 3D fusion imaging (88%; P = 0.003). The proportion in whom lesions were both detected and the distribution correctly assessed as WACA or ostial was higher with 3D fusion imaging compared to LGE imaging (54% vs 28%; P = 0.014). There was no difference in the detection of radiofrequency ablation lesions compared to cryoablation lesions (58% vs 62%; P = 1.000).

Conclusion

LGE imaging of atrial scar is not yet sufficiently accurate to reliably identify ablation lesions or to determine lesion distribution.
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Impaired eye region search accuracy in children with autistic spectrum disorders.

Open Access Issue 3 Vol 8 Published on 2013-01-01 PMID 23516446 PMCID PMC3597629
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DOI: https://doi.org/10.1371/journal.pone.0058167
Authors: John R Pruett In X Sarah Hoertel In X John N Constantino In X Angela LaMacchia Moll In X Kelly McVey In X Emma Squire In X Eric Feczko In X Daniel J Povinelli In X Steven E Petersen In X
Abstract: To explore mechanisms underlying reduced fixation of eyes in autism, children with autistic spectrum disorders (ASD) and typically developing children were tested in five visual search experiments: simple color feature; color-shape conjunction; face in non-face objects; mouth region; and eye region. No group differences were found for reaction time profile shapes in any of the five experiments, suggesting intact basic search mechanics in children with ASD. Contrary to early reports in the literature, but consistent with other more recent findings, we observed no superiority for conjunction search in children with ASD. Importantly, children with ASD did show reduced accuracy for eye region search (p = .005), suggesting that eyes contribute less to high-level face representations in ASD or that there is an eye region-specific disruption to attentional processes engaged by search in ASD.
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Global and regional left ventricular myocardial deformation measures by magnetic resonance feature tracking in healthy volunteers: comparison with tagging and relevance of gender.

Open Access Issue N/A Vol 15 Published on 2013-01-01 PMID 23331550 PMCID PMC3621526
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DOI: https://doi.org/10.1186/1532-429x-15-8
Authors: Daniel Augustine In X Adam J Lewandowski In X Merzaka Lazdam In X Aitzaz Rai In X Jane Francis In X Saul Myerson In X Alison Noble In X Harald Becher In X Stefan Neubauer In X Steffen E Petersen In X Paul Leeson In X
Abstract:

Background

Feature tracking software offers measurements of myocardial strain, velocities and displacement from cine cardiovascular magnetic resonance (CMR) images. We used it to record deformation parameters in healthy adults and compared values to those obtained by tagging.

Methods

We used TomTec 2D Cardiac Performance Analysis software to derive global, regional and segmental myocardial deformation parameters in 145 healthy volunteers who had steady state free precession (SSFP) cine left ventricular short (basal, mid and apical levels) and long axis views (horizontal long axis, vertical long axis and left ventricular out flow tract) obtained on a 1.5 T Siemens Sonata scanner. 20 subjects also had tagged acquisitions and we compared global and regional deformation values obtained from these with those from Feature Tracking.

Results

For globally averaged measurements of strain, only those measured circumferentially in short axis slices showed reasonably good levels of agreement between FT and tagging (limits of agreement -0.06 to 0.04). Longitudinal strain showed wide limits of agreement (-0.16 to 0.03) with evidence of overestimation of strain by FT relative to tagging as the mean of both measures increased. Radial strain was systematically overestimated by FT relative to tagging with very wide limits of agreement extending to as much as 100% of the mean value (-0.01 to 0.23). Reproducibility showed similar relative trends with acceptable global inter-observer variability for circumferential measures (coefficient of variation 4.9%) but poor reproducibility in the radial direction (coefficient of variation 32.3%). Ranges for deformation parameters varied between basal, mid and apical LV levels with higher levels at base compared to apex, and between genders by both FT and tagging.

Conclusions

FT measurements of circumferential but not longitudinally or radially directed global strain showed reasonable agreement with tagging and acceptable inter-observer reproducibility. We record provisional ranges of FT deformation parameters at global, regional and segmental levels. They show evidence of variation with gender and myocardial region in the volunteers studied, but have yet to be compared with tagging measurements at the segmental level.
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Raised troponin in COPD: clinical implications and possible mechanisms.

Issue 2 Vol 99 Published on 2013-01-01 PMID 23184012 PMCID N/A
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DOI: https://doi.org/10.1136/heartjnl-2012-302969
Authors: Ian S Stone In X Steffen E Petersen In X Neil C Barnes In X
Abstract: No Abstract Available
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Gender-specific differences in left ventricular remodelling in obesity: insights from cardiovascular magnetic resonance imaging.

Issue 4 Vol 34 Published on 2013-01-01 PMID 23053174 PMCID PMC3549525
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DOI: https://doi.org/10.1093/eurheartj/ehs341
Authors: Oliver J Rider In X Adam Lewandowski In X Richard Nethononda In X Steffen E Petersen In X Jane M Francis In X Alex Pitcher In X Cameron J Holloway In X Sairia Dass In X Rajarshi Banerjee In X James P Byrne In X Paul Leeson In X Stefan Neubauer In X
Abstract:

Aims

As obesity-related cardiovascular mortality, although elevated when compared with normal weight, is lower in females than in males at every body mass index (BMI) level, we aimed to investigate gender-specific differences in left ventricular (LV) hypertrophy in obesity, which themselves have been shown to have varying prognostic value.

Method and results

In total, 741 subjects (female, n = 399) without identifiable cardiovascular risk factors (BMI 15.7-59.2 kg/m(2)) underwent cardiovascular magnetic resonance (1.5 T) to determine LV mass, end-diastolic volume (EDV, mL), and LV mass/volume ratio (LVM/VR). Across both sexes, there was a strong positive correlation between BMI and LV mass (male r = 0.44, female r = 0.57, both P < 0.001), with males showing a greater LV hypertrophic response (male +2.3 vs. female +1.6 g per BMI point increase, P = 0.001). Concentric hypertrophy was present in both sexes and LVM/VR positively correlated to BMI (male r = 0.45, female r = 0.29, both P < 0.001) on linear regression analysis. However, the degree of concentric hypertrophy was greater in males (male +0.13 vs. female +0.06 LVM/VR increase per BMI point increase, P = 0.001). On the other hand, females showed a greater LV cavity dilatory response (female +1.1 vs. male +0.3 mL per BMI point increase, P < 0.001). Indeed, in contrast to females, where BMI and LV-EDV were positively correlated (r = 0.38, P < 0.001), BMI did not correlate with EDV in men (r = 0.03, P = 0.62).

Conclusion

In the absence of traditional cardiovascular risk factors, obese men show predominantly concentric hypertrophy, whereas obese women exhibit both eccentric and concentric hypertrophy. As concentric hypertrophy is more strongly related to cardiovascular mortality than eccentric hypertrophy, our observations may explain the observed gender difference in obesity-related mortality.
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Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking.

Issue 1 Vol 18 Published on 2013-01-01 PMID 22340136 PMCID PMC3470739
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DOI: https://doi.org/10.1111/j.1369-1600.2012.00435.x
Authors: Christina N Lessov-Schlaggar In X Rebecca L Lepore In X Sean D Kristjansson In X Bradley L Schlaggar In X Kelly Anne Barnes In X Steven E Petersen In X Pamela A F Madden In X Andrew C Heath In X Deanna M Barch In X
Abstract: Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (24-34 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked ≥100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems.
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Is there a role for stress CMR in stable chest pain with >60% predicted risk of coronary artery disease?

Issue 12 Vol 105 Published on 2012-12-01 PMID 23132953 PMCID N/A
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DOI: https://doi.org/10.1093/qjmed/hcs218
Authors: Amardeep Ghosh Dastidar In X Francesca Pugliese In X Ceri Davies In X Mark Westwood In X Adam Timmis In X Andrew Wragg In X Steffen E Petersen In X
Abstract: No Abstract Available
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The left occipitotemporal cortex does not show preferential activity for words.

Issue 12 Vol 22 Published on 2012-12-01 PMID 22235035 PMCID PMC3491762
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DOI: https://doi.org/10.1093/cercor/bhr295
Authors: Alecia C Vogel In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high-spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters.
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The hemodynamic response in children with Simplex Autism.

Issue 4 Vol 2 Published on 2012-10-01 PMID 22795455 PMCID PMC3603569
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DOI: https://doi.org/10.1016/j.dcn.2012.06.001
Authors: Eric Feczko In X Francis M Miezin In X John N Constantino In X Bradley L Schlaggar In X Steven E Petersen In X John R Pruett In X
Abstract:

Background

Numerous functional magnetic resonance imaging (fMRI) studies of the brain-bases of autism have demonstrated altered cortical responses in subjects with autism, relative to typical subjects, during a variety of tasks. These differences may reflect altered neuronal responses or altered hemodynamic response. This study searches for evidence of hemodynamic response differences by using a simple visual stimulus and elementary motor actions, which should elicit similar neuronal responses in patients and controls.

Methods

We acquired fMRI data from two groups of 16 children, a typical group and a group with Simplex Autism, during a simple visuomotor paradigm previously used to assess this question in other cross-group comparisons. A general linear model estimated the blood-oxygen-level-dependent (BOLD) signal time course, and repeated-measures analysis of variance tested for potential cross-group differences in the BOLD signal.

Results

The hemodynamic response in Simplex Autism is similar to that found in typical children. Although the sample size was small for a secondary analysis, medication appeared to have no effect on the hemodynamic response within the Simplex Autism group.

Conclusions

When fMRI studies show BOLD response differences between autistic and typical subjects, these results likely reflect between-group differences in neural activity and not an altered hemodynamic response.
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The Human Connectome Project: a data acquisition perspective.

Issue 4 Vol 62 Published on 2012-10-01 PMID 22366334 PMCID PMC3606888
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DOI: https://doi.org/10.1016/j.neuroimage.2012.02.018
Authors: D C Van Essen In X K Ugurbil In X E Auerbach In X D Barch In X T E J Behrens In X R Bucholz In X A Chang In X L Chen In X M Corbetta In X S W Curtiss In X S Della Penna In X D Feinberg In X M F Glasser In X N Harel In X A C Heath In X L Larson-Prior In X D Marcus In X G Michalareas In X S Moeller In X R Oostenveld In X S E Petersen In X F Prior In X B L Schlaggar In X S M Smith In X A Z Snyder In X J Xu In X E Yacoub In X In X
Abstract: The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.
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In favor of a 'fractionation' view of ventral parietal cortex: comment on Cabeza et al.

Issue 8 Vol 16 Published on 2012-08-01 PMID 22795558 PMCID N/A
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DOI: https://doi.org/10.1016/j.tics.2012.06.014
Authors: Steven M Nelson In X Kathleen B McDermott In X Steven E Petersen In X
Abstract: No Abstract Available
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The mixed block/event-related design.

Issue 2 Vol 62 Published on 2012-08-01 PMID 22008373 PMCID PMC3288695
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DOI: https://doi.org/10.1016/j.neuroimage.2011.09.084
Authors: Steven E Petersen In X Joseph W Dubis In X
Abstract: Neuroimaging studies began using block design and event-related design experiments. While providing many insights into brain functions, these fMRI design types ignore components of the BOLD signal that can teach us additional elements. The development of the mixed block/event-related fMRI design allowed for a fuller characterization of nonlinear and time-sensitive neuronal responses: for example, the interaction between block and event related factors and the simultaneous extraction of transient activity related to trials and block transitions and sustained activity related to task-level processing. This review traces the origins of the mixed block/event-related design from conceptual precursors to a seminal paper and on to subsequent studies using the method. The review also comments on aspects of the experimental design that must be considered when attempting to use the mixed block/event-related design. When taking into account these considerations, the mixed block/event-related design allows fuller utilization of the BOLD signal allowing deeper interpretation of how regions of the brain function on multiple timescales.
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Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease?

Issue 14 Vol 98 Published on 2012-07-01 PMID 22739636 PMCID N/A
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DOI: https://doi.org/10.1136/heartjnl-2012-301759
Authors: Ian S Stone In X Neil C Barnes In X Steffen E Petersen In X
Abstract: Significant cardiac morbidity and mortality exists in patients with COPD. Shared risk factors include age, smoking history and exposure to air pollution and passive smoke. Although the inappropriate under-prescribing of β-blockers contributes, it is now appreciated that the observed cardiac risk is not only due to smoking and conventional cardiovascular risk factors, but also other independent factors. A number of hypotheses exist for the increased cardiovascular morbidity and mortality seen in COPD including inflammation, pulmonary hypertension, lung hyperinflation and shared genetics models. Mounting evidence from large randomised controlled trials suggests that COPD treatment may be cardio-protective. We review the current evidence supporting the aforementioned hypotheses and how their modulation may prevent cardiovascular morbidity and mortality in COPD. The persisting underdiagnosis of COPD may have significant consequences. Further mechanistic studies identifying the onset and impact of individual interventions will develop our understanding of this emerging and highly relevant clinical field.
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ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS 2012 appropriate use criteria for peripheral vascular ultrasound and physiological testing part I: arterial ultrasound and physiological testing: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American College of Radiology, American Institute of Ultrasound in Medicine, American Society of Echocardiography, American Society of Nephrology, Intersocietal Commission for the Accreditation of Vascular Laboratories, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery.

Issue 1 Vol 56 Published on 2012-07-01 PMID 22694919 PMCID PMC4514917
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DOI: https://doi.org/10.1016/j.jvs.2012.05.054
Authors: In X In X In X In X In X In X In X In X In X In X In X In X In X In X In X In X In X Emile R Mohler In X Heather L Gornik In X Marie Gerhard-Herman In X Sanjay Misra In X Jeffrey W Olin In X Eugene Zierler In X
Abstract: No Abstract Available
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ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS/SVU [corrected] 2012 appropriate use criteria for peripheral vascular ultrasound and physiological testing part I: arterial ultrasound and physiological testing: a report of the American College of Cardiology Foundation appropriate use criteria task force, American College of Radiology, American Institute of Ultrasound in Medicine, American Society of Echocardiography, American Society of Nephrology, Intersocietal Commission for the Accreditation of Vascular Laboratories, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Interventional Radiology, Society for Vascular Medicine, Society for Vascular Surgery, [corrected] and Society for Vascular Ultrasound. [corrected].

Issue 3 Vol 60 Published on 2012-07-01 PMID 22694840 PMCID PMC4634367
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Keywords:
DOI: https://doi.org/10.1016/j.jacc.2012.02.009
Authors: In X In X In X In X In X In X In X In X In X In X In X Emile R Mohler In X Heather L Gornik In X Marie Gerhard-Herman In X Sanjay Misra In X Jeffrey W Olin In X R Eugene Zierler In X Michael J Wolk In X Emile R Mohler In X
Abstract: No Abstract Available
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Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.

Open Access Issue N/A Vol 344 Published on 2012-06-01 PMID 22692650 PMCID PMC3374026
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Keywords:
DOI: https://doi.org/10.1136/bmj.e3485
Authors: Tessa S S Genders In X Ewout W Steyerberg In X M G Myriam Hunink In X Koen Nieman In X Tjebbe W Galema In X Nico R Mollet In X Pim J de Feyter In X Gabriel P Krestin In X Hatem Alkadhi In X Sebastian Leschka In X Lotus Desbiolles In X Matthijs F L Meijs In X Maarten J Cramer In X Juhani Knuuti In X Sami Kajander In X Jan Bogaert In X Kaatje Goetschalckx In X Filippo Cademartiri In X Erica Maffei In X Chiara Martini In X Sara Seitun In X Annachiara Aldrovandi In X Simon Wildermuth In X Björn Stinn In X Jürgen Fornaro In X Gudrun Feuchtner In X Tobias De Zordo In X Thomas Auer In X Fabian Plank In X Guy Friedrich In X Francesca Pugliese In X Steffen E Petersen In X L Ceri Davies In X U Joseph Schoepf In X Garrett W Rowe In X Carlos A G van Mieghem In X Luc van Driessche In X Valentin Sinitsyn In X Deepa Gopalan In X Konstantin Nikolaou In X Fabian Bamberg In X Ricardo C Cury In X Juan Battle In X Pál Maurovich-Horvat In X Andrea Bartykowszki In X Bela Merkely In X Dávid Becker In X Martin Hadamitzky In X Jörg Hausleiter In X Marc Dewey In X Elke Zimmermann In X Michael Laule In X
Abstract:

Objectives

To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations.

Design

Retrospective pooled analysis of individual patient data.

Setting

18 hospitals in Europe and the United States.

Participants

Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively).

Main outcome measures

Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined.

Results

We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory.

Conclusions

Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.
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Parcellation in left lateral parietal cortex is similar in adults and children.

Issue 5 Vol 22 Published on 2012-05-01 PMID 21810781 PMCID PMC3328346
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Keywords:
DOI: https://doi.org/10.1093/cercor/bhr189
Authors: Kelly Anne Barnes In X Steven M Nelson In X Alexander L Cohen In X Jonathan D Power In X Rebecca S Coalson In X Francis M Miezin In X Alecia C Vogel In X Joseph W Dubis In X Jessica A Church In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.
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Comment on "The physiology of developmental changes in BOLD functional imaging signals" by Harris, Reynell, and Attwell.

Issue 2 Vol 2 Published on 2012-04-01 PMID 22483071 PMCID PMC4034377
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DOI: https://doi.org/10.1016/j.dcn.2011.10.003
Authors: Jessica A Church In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: No Abstract Available
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Effect of mechanical brushing on survival and hemodynamic characteristics of tunneled hemodialysis catheters.

Issue 2 Vol 13 Published on 2012-04-01 PMID 22266590 PMCID N/A
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DOI: https://doi.org/10.5301/jva.5000045
Authors: Niels Henrik Buus In X Thomas Granum Aagaard In X Agnete Hauge Mortensen In X Jens dam Jensen In X Ulla Møldrup In X Steffen Ellebæk Petersen In X
Abstract:

Purpose

Tunneled catheters used for hemodialysis treatment often become dysfunctional due to deposition of clotting material within the catheter lumen. In a retrospective study design we investigated the effect of mechanical brushing of dysfunctional tunneled catheters using a metal guide wire with simultaneous installation of urokinase.

Materials and methods

During a period of 26 months all together 24 different catheters in 21 chronic hemodialysis patients were brushed due to insufficient blood flow or increased arterial or venous line pressures resulting in repeated alarms during dialysis treatments.

Results

Median functional survival after brushing was 45 days with 8 catheters being exchanged (n=5) or rebrushed (n=3) within 10 dialysis sessions (4 weeks). After 2 months all together 13 (54%) catheters were exchanged due to repeated dysfunction and by 3 months functional survival was only about 35%. The catheters needing exchange were characterized by low flow and high arterial line resistance already in the dialysis sessions immediately following the brushing procedure. Median survival of the exchanged catheters was considerably longer (>400 days) as compared to the brushed catheters.

Conclusions

In conclusion mechanical brushing of dysfunctional tunneled hemodialysis catheters can prolong short term function but only affects long term catheter survival in a minority of the patients.
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The putative visual word form area is functionally connected to the dorsal attention network.

Issue 3 Vol 22 Published on 2012-03-01 PMID 21690259 PMCID PMC3278314
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Keywords:
DOI: https://doi.org/10.1093/cercor/bhr100
Authors: Alecia C Vogel In X Fran M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The putative visual word form area (pVWFA) is the most consistently activated region in single word reading studies (i.e., Vigneau et al. 2006), yet its function remains a matter of debate. The pVWFA may be predominantly used in reading or it could be a more general visual processor used in reading but also in other visual tasks. Here, resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) is used to characterize the functional relationships of the pVWFA to help adjudicate between these possibilities. rs-fcMRI defines relationships based on correlations in slow fluctuations of blood oxygen level-dependent activity occurring at rest. In this study, rs-fcMRI correlations show little relationship between the pVWFA and reading-related regions but a strong relationship between the pVWFA and dorsal attention regions thought to be related to spatial and feature attention. The rs-fcMRI correlations between the pVWFA and regions of the dorsal attention network increase with age and reading skill, while the correlations between the pVWFA and reading-related regions do not. These results argue the pVWFA is not used predominantly in reading but is a more general visual processor used in other visual tasks, as well as reading.
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Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion.

Issue 3 Vol 59 Published on 2012-02-01 PMID 22019881 PMCID PMC3254728
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DOI: https://doi.org/10.1016/j.neuroimage.2011.10.018
Authors: Jonathan D Power In X Kelly A Barnes In X Abraham Z Snyder In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Here, we demonstrate that subject motion produces substantial changes in the timecourses of resting state functional connectivity MRI (rs-fcMRI) data despite compensatory spatial registration and regression of motion estimates from the data. These changes cause systematic but spurious correlation structures throughout the brain. Specifically, many long-distance correlations are decreased by subject motion, whereas many short-distance correlations are increased. These changes in rs-fcMRI correlations do not arise from, nor are they adequately countered by, some common functional connectivity processing steps. Two indices of data quality are proposed, and a simple method to reduce motion-related effects in rs-fcMRI analyses is demonstrated that should be flexibly implementable across a variety of software platforms. We demonstrate how application of this technique impacts our own data, modifying previous conclusions about brain development. These results suggest the need for greater care in dealing with subject motion, and the need to critically revisit previous rs-fcMRI work that may not have adequately controlled for effects of transient subject movements.
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The attention system of the human brain: 20 years after.

Issue N/A Vol 35 Published on 2012-01-01 PMID 22524787 PMCID PMC3413263
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DOI: https://doi.org/10.1146/annurev-neuro-062111-150525
Authors: Steven E Petersen In X Michael I Posner In X
Abstract: Here, we update our 1990 Annual Review of Neuroscience article, "The Attention System of the Human Brain." The framework presented in the original article has helped to integrate behavioral, systems, cellular, and molecular approaches to common problems in attention research. Our framework has been both elaborated and expanded in subsequent years. Research on orienting and executive functions has supported the addition of new networks of brain regions. Developmental studies have shown important changes in control systems between infancy and childhood. In some cases, evidence has supported the role of specific genetic variations, often in conjunction with experience, that account for some of the individual differences in the efficiency of attentional networks. The findings have led to increased understanding of aspects of pathology and to some new interventions.
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Computational fluid dynamics simulation of a-v fistulas: from MRI and ultrasound scans to numeric evaluation of hemodynamics.

Issue 1 Vol 13 Published on 2012-01-01 PMID 21725950 PMCID N/A
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DOI: https://doi.org/10.5301/jva.2011.8440
Authors: Anders Koustrup Niemann In X Samuel Thrysoe In X Jens Vinge Nygaard In X John Michael Hasenkam In X Steffen Ellebaek Petersen In X
Abstract:

Purpose

A-v anastomosis entails dramatic changes in hemodynamic conditions, which may lead to major alterations to the vessels involved; primarily dilatations and devastating stenoses. Wall shear stress is thought to play a key role in the remodeling of the vessels exposed to abnormal levels and oscillating wall shear stress. In this study we sought to develop a framework suitable for thorough in vivo analyses of wall shear stress and vessel morphology of a-v fistulas in patients.

Methods

Using ultrasound and magnetic resonance imaging (MRI) transverse image stacks from six patient a-v fistulas were obtained. From the image stacks three-dimensional geometries of the patient fistulas were created using dedicated segmentation software. Geometries of three a-v fistulas were imported into finite element software in order to perform fluid flow simulations of blood flows and frictional forces on the vessel walls in the a-v fistulas. Boundary conditions for the simulations were obtained using both a MRI phase contrast and an ultrasound Doppler technique.

Results

The segmentation of the six fistulas of very different age and morphology (two end-to-side and four side-to-side) showed the ability of the approach to create geometries of various fistula morphologies. Simulations of the three fistulas showed an instant picture of the present status of the exposure to different levels of wall shear stress and the morphological status in the vessel remodeling process.

Conclusion

The study demonstrated the capability of the CFD framework to analyze patient a-v fistulas on a regular basis using both MRI and ultrasound-based approaches.
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Functional network organization of the human brain.

Issue 4 Vol 72 Published on 2011-11-01 PMID 22099467 PMCID PMC3222858
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DOI: https://doi.org/10.1016/j.neuron.2011.09.006
Authors: Jonathan D Power In X Alexander L Cohen In X Steven M Nelson In X Gagan S Wig In X Kelly Anne Barnes In X Jessica A Church In X Alecia C Vogel In X Timothy O Laumann In X Fran M Miezin In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a "processing" system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex.
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Late gadolinium enhancement CMR predicts adverse cardiovascular outcomes and mortality in patients with coronary artery disease: systematic review and meta-analysis.

Issue 3 Vol 54 Published on 2011-11-01 PMID 22014489 PMCID N/A
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DOI: https://doi.org/10.1016/j.pcad.2011.07.003
Authors: Filip Zemrak In X Steffen E Petersen In X
Abstract: Cardiovascular magnetic resonance (CMR) has a recognized role in diagnosing and monitoring coronary artery disease (CAD). Multiple studies have shown that CMR can predict adverse outcomes. We reviewed contemporary available literature to establish the role of CMR with late gadolinium enhancement (LGE) in predicting mortality and major adverse cardiac events (MACEs) in patients with CAD. Meta-analysis of available prospective studies showed that the presence of LGE increases the hazards of death by more than 4 times and of MACE by almost 4 times. The size of LGE (per gram or percent) increases the hazards of death and MACE by 4% and 5%, respectively. The presence and size of LGE predict mortality and MACE in CAD. Various parameters derived from LGE images enhance the predictive value. Large randomized controlled trials are needed to establish the actual value of LGE and other derived parameters in the wider population.
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Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints.

Open Access Issue 16 Vol 97 Published on 2011-08-01 PMID 21715443 PMCID PMC3142342
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DOI: https://doi.org/10.1136/hrt.2011.225904
Authors: Alex Pitcher In X Deborah Ashby In X Paul Elliott In X Steffen E Petersen In X
Abstract: Recent advances in cardiovascular magnetic resonance (CMR) now allow the accurate and reproducible measurement of many aspects of cardiac and vascular structure and function, with prognostic data emerging for several key imaging biomarkers. These biomarkers are increasingly used in the evaluation of new drugs, devices and lifestyle modifications for the prevention and treatment of cardiovascular disease. This review outlines a conceptual framework for the application of imaging biomarkers to clinical trials, highlights several important CMR techniques which are in use in randomised studies, and reviews certain aspects of trial design, conduct and interpretation in relation to the use of CMR.
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Contrast-enhanced CMR in patients after percutaneous closure of the left atrial appendage: a pilot study.

Open Access Issue N/A Vol 13 Published on 2011-07-01 PMID 21726450 PMCID PMC3146401
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DOI: https://doi.org/10.1186/1532-429x-13-33
Authors: Oliver K Mohrs In X Nina Wunderlich In X Steffen E Petersen In X Anselm Pottmeyer In X Hans-Ulrich Kauczor In X
Abstract:

Background

To evaluate the feasibility and value of first-pass contrast-enhanced dynamic and post-contrast 3D CMR in patients after transcatheter occlusion of left atrial appendage (LAA) to identify incorrect placement and persistent leaks.

Methods

7 patients with different occluder systems (n = 4 PLAATO; n = 2 Watchman; n = 1 ACP) underwent 2 contrast-enhanced (Gd-DOTA) CMR sequences (2D TrueFISP first-pass perfusion and 3D-TurboFLASH) to assess localization, artifact size and potential leaks of the devices. Perfusion CMR was analyzed visually and semi-quantitatively to identify potential leaks.

Results

All occluders were positioned within the LAA. The ACP occluder presented the most extensive artifact size. Visual assessment revealed a residual perfusion of the LAA apex in 4 cases using first-pass perfusion and 3D-TurboFLASH indicating a suboptimal LAA occlusion.By assessing signal-to-time-curves the cases with a visually detected leak showed a 9-fold higher signal-peak in the LAA apex (567 ± 120% increase from baseline signal) than those without a leak (61 ± 22%; p < 0.03). In contrast, the signal increase in LAA proximal to the occluder showed no difference (leak 481 ± 201% vs. no leak 478 ± 125%; p = 0.48).

Conclusion

This CMR pilot study provides valuable non-invasive information in patients after transcatheter occlusion of the LAA to identify correct placement and potential leaks. We recommend incorporating CMR in future clinical studies to evaluate new device types.
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Social and non-social cueing of visuospatial attention in autism and typical development.

Issue 6 Vol 41 Published on 2011-06-01 PMID 20809377 PMCID PMC3660145
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DOI: https://doi.org/10.1007/s10803-010-1090-z
Authors: John R Pruett In X Angela LaMacchia In X Sarah Hoertel In X Emma Squire In X Kelly McVey In X Richard D Todd In X John N Constantino In X Steven E Petersen In X
Abstract: Three experiments explored attention to eye gaze, which is incompletely understood in typical development and is hypothesized to be disrupted in autism. Experiment 1 (n = 26 typical adults) involved covert orienting to box, arrow, and gaze cues at two probabilities and cue-target times to test whether reorienting for gaze is endogenous, exogenous, or unique; experiment 2 (total n = 80: male and female children and adults) studied age and sex effects on gaze cueing. Gaze cueing appears endogenous and may strengthen in typical development. Experiment 3 tested exogenous, endogenous, and gaze-based orienting in 25 typical and 27 Autistic Spectrum Disorder (ASD) children. ASD children made more saccades, slowing their reaction times; however, exogenous and endogenous orienting, including gaze cueing, appear intact in ASD.
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Manipulation of length and lexicality localizes the functional neuroanatomy of phonological processing in adult readers.

Issue 6 Vol 23 Published on 2011-06-01 PMID 20433237 PMCID PMC2991592
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DOI: https://doi.org/10.1162/jocn.2010.21515
Authors: Jessica A Church In X David A Balota In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: In a previous study of single word reading, regions in the left supramarginal gyrus and left angular gyrus showed positive BOLD activity in children but significantly less activity in adults for high-frequency words [Church, J. A., Coalson, R. S., Lugar, H. M., Petersen, S. E., & Schlaggar, B. L. A developmental fMRI study of reading and repetition reveals changes in phonological and visual mechanisms over age. Cerebral Cortex, 18, 2054-2065, 2008]. This developmental decrease may reflect decreased reliance on phonological processing for familiar stimuli in adults. Therefore, in the present study, variables thought to influence phonological demand (string length and lexicality) were manipulated. Length and lexicality effects in the brain were explored using both ROI and whole-brain approaches. In the ROI analysis, the supramarginal and angular regions from the previous study were applied to this study. The supramarginal region showed a significant positive effect of length, consistent with a role in phonological processing, whereas the angular region showed only negative deflections from baseline with a strong effect of lexicality and other weaker effects. At the whole-brain level, varying effects of length and lexicality and their interactions were observed in 85 regions throughout the brain. The application of hierarchical clustering analysis to the BOLD time course data derived from these regions revealed seven clusters, with potentially revealing anatomical locations. Of note, a left angular gyrus region was the sole constituent of one cluster. Taken together, these findings in adult readers (1) provide support for a widespread set of brain regions affected by lexical variables, (2) corroborate a role for phonological processing in the left supramarginal gyrus, and (3) do not support a strong role for phonological processing in the left angular gyrus.
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Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure.

Issue 5 Vol 50 Published on 2011-05-01 PMID 21515200 PMCID PMC3082744
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DOI: https://doi.org/10.1016/j.jaac.2011.01.009
Authors: Natasha Marrus In X Carley Faughn In X Jeremy Shuman In X Steve E Petersen In X John N Constantino In X Daniel J Povinelli In X John R Pruett In X
Abstract:

Objective

Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure.

Method

We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimpanzee SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n = 29) with the Chimpanzee SRS and typical and human children with autism spectrum disorder (ASD; n = 20) with the XSRS.

Results

The Chimpanzee SRS demonstrated strong interrater reliability at the three sites (ranges for individual ICCs: 0.534 to 0.866; mean ICCs: 0.851 to 0.970). As has been observed in human beings, exploratory principal components analysis of Chimpanzee SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r = 0.976, p = .001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees.

Conclusion

Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) human beings and chimpanzees.
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Concepts and principles in the analysis of brain networks.

Issue N/A Vol 1224 Published on 2011-04-01 PMID 21486299 PMCID N/A
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DOI: https://doi.org/10.1111/j.1749-6632.2010.05947.x
Authors: Gagan S Wig In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The brain is a large-scale network, operating at multiple levels of information processing ranging from neurons, to local circuits, to systems of brain areas. Recent advances in the mathematics of graph theory have provided tools with which to study networks. These tools can be employed to understand how the brain's behavioral repertoire is mediated by the interactions of objects of information processing. Within the graph-theoretic framework, networks are defined by independent objects (nodes) and the relationships shared between them (edges). Importantly, the accurate incorporation of graph theory into the study of brain networks mandates careful consideration of the assumptions, constraints, and principles of both the mathematics and the underlying neurobiology. This review focuses on understanding these principles and how they guide what constitutes a brain network and its elements, specifically focusing on resting-state correlations in humans. We argue that approaches that fail to take the principles of graph theory into consideration and do not reflect the underlying neurobiological properties of the brain will likely mischaracterize brain network structure and function.
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With the "universal definition," measurement of creatine kinase-myocardial band rather than troponin allows more accurate diagnosis of periprocedural necrosis and infarction after coronary intervention.

Issue 6 Vol 57 Published on 2011-02-01 PMID 21292125 PMCID N/A
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DOI: https://doi.org/10.1016/j.jacc.2010.07.058
Authors: Chris C S Lim In X William J van Gaal In X Luca Testa In X Florim Cuculi In X Jayanth R Arnold In X Theodoros Karamitsos In X Jane M Francis In X Steffen E Petersen In X Janet E Digby In X Stephen Westaby In X Charalambos Antoniades In X Rajesh K Kharbanda In X Louise M Burrell In X Stefan Neubauer In X Adrian P Banning In X
Abstract:

Objectives

We aimed to assess the differential implications of creatine kinase-myocardial band (CK-MB) and troponin measurement with the universal definition of periprocedural injury after percutaneous coronary intervention.

Background

Differentiation between definitions of periprocedural necrosis and periprocedural infarction has practical, sociological, and research implications. Troponin is the recommended biomarker, but there has been debate about the recommended diagnostic thresholds.

Methods

Thirty-two patients undergoing multivessel percutaneous coronary intervention and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging in a prospective study had cardiac troponin I, CK-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, tumor necrosis factor alpha) measured at baseline, 1 h, 6 h, 12 h, and 24 h after the procedure. Three "periprocedural injury" groups were defined with the universal definition: G1: no injury (biomarker <99th percentile); G2: periprocedural necrosis (1 to 3 × 99th percentile); G3: myocardial infarction (MI) type 4a (>3 × 99th percentile). Differences in inflammatory profiles were analyzed.

Results

With CK-MB there were 17, 10, and 5 patients in groups 1, 2, and 3, respectively. Patients with CK-MB-defined MI type 4a closely approximated patients with new CMR-LGE injury. Groups defined with CK-MB showed progressively increasing percentage change in C-reactive protein and serum amyloid A, reflecting increasing inflammatory response (p < 0.05). Using cardiac troponin I resulted in 26 patients defined as MI type 4a, but only a small minority had evidence of abnormality on CMR-LGE, and only 3 patients were defined as necrosis. No differences in inflammatory response were evident when groups were defined with troponin.

Conclusions

Measuring CK-MB is more clinically relevant for diagnosing MI type 4a, when applying the universal definition. Current troponin thresholds are oversensitive with the arbitrary limit of 3 × 99th percentile failing to discriminate between periprocedural necrosis and MI type 4a. (Myocardial Injury following Coronary Artery bypass Surgery versus Angioplasty: a randomised controlled trial using biochemical markers and cardiovascular magnetic resonance imaging; ISRCTN25699844).
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High-resolution 3D non-contrast-enhanced, ECG-gated, multi-step MR angiography of the lower extremities: comparison with contrast-enhanced MR angiography.

Issue 2 Vol 21 Published on 2011-02-01 PMID 20706840 PMCID N/A
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DOI: https://doi.org/10.1007/s00330-010-1932-2
Authors: Oliver K Mohrs In X Steffen E Petersen In X Martin C Heidt In X Thomas Schulze In X Peter Schmitt In X Sabine Bergemann In X Hans-Ulrich Kauczor In X
Abstract:

Objective

To determine the diagnostic value of non-contrast-enhanced, 3D-high-resolution, ECG-gated, multi-step MR angiography (non-ceMRA) of the lower extremities using a modified turbo-spin-echo technique in comparison to 1.0-molar contrast-enhanced MR angiography (ceMRA) in patients with suspected peripheral vascular disease (PVD).

Methods

Fifty consecutive patients underwent non-ceMRA before ceMRA within the same session. We assessed examination time, image quality, localisation and severity of stenosis.

Results

Examination time was shorter for ceMRA (12 ± 4 min) compared with non-ceMRA (28 ± 6 min, p < 0.001). The image quality of the aorta-iliac, femoral and combined popliteal and lower leg arteries was inferior for non-ceMRA (2.8 ± 0.8/3.3 ± 0.8/3.3 ± 0.9) versus ceMRA (4.7 ± 0.8/4.8 ± 0.6/4.8 ± 0.7) on a 5-point scale with 5 for maximum quality (p < 0.01). CeMRA offered more assessable data sets than non-ceMRA (98% vs. 90%). For detecting stenosis >50% or occlusions of pelvic and femoral arteries using non-ceMRA the sensitivity, specificity, positive and negative predictive values were 94%, 86%, 67% and 98% and for popliteal and lower leg arteries 93%, 87%, 69% and 98%, respectively.

Conclusion

We demonstrated that 3D non-ceMRA represents a very promising technique in patients with lower extremities PVD and could be used as an alternative if gadolinium-based contrast agents cannot be administered.
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Ventricular hypertrophy and cavity dilatation in relation to body mass index in women with uncomplicated obesity.

Issue 3 Vol 97 Published on 2011-02-01 PMID 20483890 PMCID N/A
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DOI: https://doi.org/10.1136/hrt.2009.185009
Authors: Oliver J Rider In X Steffen E Petersen In X Jane M Francis In X Mohammed K Ali In X Lucy E Hudsmith In X Monique R Robinson In X Kieran Clarke In X Stefan Neubauer In X
Abstract:

Objective

The traditionally accepted mechanism for ventricular adaptation to obesity suggests that cavity dilatation in response to increased blood volume and elevated filling pressure results in ventricular hypertrophy as a compensatory mechanism. Our hypothesis was that, instead, initiation of ventricular hypertrophy in obesity may be explained by changes in hormonal milieu and not by cavity dilatation.

Research design and methods

88 female subjects without identifiable cardiovascular risk factors, covering a wide range of body mass indices (BMI), from normal (21.2 ± 1.6 kg/m(2)) to severely obese (45.0 ± 4.6 kg/m(2)), underwent cardiovascular MRI to determine left ventricular (LV) and right ventricular (RV) mass and volumes.

Results

BMI correlated positively with LV and RV mass and end-diastolic volumes (EDV). However overweight is associated with a significant LV and RV hypertrophy (LV: 78 ± 11 g vs 103 ± 16 g, p<0.01; RV: 26 ± 7 g vs 40 ± 11 g, p<0.01) was observed in the absence of differences in LV and RV volumes (LV: EDV 119 ± 15 vs 121 ± 21 ml, p>0.99, RV: 131 ± 17 vs 130 ± 24 ml; p>0.99). Furthermore, significant increases of serum leptin occurred at this pre-obese stage (15.6 ± 19 vs 36.5 ± 22 ng/ml; p=0.013).

Conclusion

In a cohort of healthy female subjects with a wide range of BMIs, ventricular hypertrophy occurs without associated cavity dilatation in overweight individuals, while in manifest obesity, both cavity dilatation and ventricular hypertrophy occur. Elevated leptin levels may have a role in this effect on ventricular mass.
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Modulation of the brain's functional network architecture in the transition from wake to sleep.

Issue N/A Vol 193 Published on 2011-01-01 PMID 21854969 PMCID PMC3811144
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DOI: https://doi.org/10.1016/b978-0-444-53839-0.00018-1
Authors: Linda J Larson-Prior In X Jonathan D Power In X Justin L Vincent In X Tracy S Nolan In X Rebecca S Coalson In X John Zempel In X Abraham Z Snyder In X Bradley L Schlaggar In X Marcus E Raichle In X Steven E Petersen In X
Abstract: The transition from quiet wakeful rest to sleep represents a period over which attention to the external environment fades. Neuroimaging methodologies have provided much information on the shift in neural activity patterns in sleep, but the dynamic restructuring of human brain networks in the transitional period from wake to sleep remains poorly understood. Analysis of electrophysiological measures and functional network connectivity of these early transitional states shows subtle shifts in network architecture that are consistent with reduced external attentiveness and increased internal and self-referential processing. Further, descent to sleep is accompanied by the loss of connectivity in anterior and posterior portions of the default-mode network and more locally organized global network architecture. These data clarify the complex and dynamic nature of the transitional period between wake and sleep and suggest the need for more studies investigating the dynamics of these processes.
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High-resolution 3D unenhanced ECG-gated respiratory-navigated MR angiography of the renal arteries: comparison with contrast-enhanced MR angiography.

Issue 6 Vol 195 Published on 2010-12-01 PMID 21098205 PMCID N/A
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DOI: https://doi.org/10.2214/ajr.10.4365
Authors: Oliver K Mohrs In X Steffen E Petersen In X Thomas Schulze In X Michael Zieschang In X Harald Küx In X Peter Schmitt In X Sabine Bergemann In X Hans-Ulrich Kauczor In X
Abstract:

Objective

The aim of this study is to determine the diagnostic value of high-resolution 3D unenhanced ECG-gated respiratory-navigated MR angiography (MRA) of the renal arteries using a steady-state free precession (SSFP) technique in comparison with 1.0-molar contrast-enhanced MRA in patients with suspected renal artery stenosis.

Subjects and methods

Forty-five consecutive patients underwent unenhanced MRA before contrast-enhanced MRA within the same session. We assessed examination time, image quality, renal artery architecture, and localization and severity of renal artery stenosis.

Results

Examination time was shorter for contrast-enhanced MRA (mean ± SD, 12 ± 3 minutes) than for unenhanced MRA (19 ± 3 minutes; p < 0.001). On a 5-point scale, the image quality was similar for contrast-enhanced MRA (3.8 ± 1.0) and unenhanced MRA (4.0 ± 1.3; p = 0.24). Contrast-enhanced MRA offered more assessable data sets than did unenhanced MRA (95% vs 90%); however, unenhanced MRA had more data sets with maximum image quality (49% vs 30%). There was moderate agreement in stenosis grading between both MRA techniques (κ = 0.51; p < 0.001), but in only one case (1.3%) we found mismatch of more than one severity stenosis grade (stenoses > 75%). Sensitivity, specificity, and positive and negative predictive values of unenhanced MRA to detect renal artery stenoses greater than 50% were 75%, 99%, 75%, and 99%, respectively.

Conclusion

We show that SSFP 3D unenhanced MRA is a very promising technique for patients with suspected renovascular disease and could be used as an alternative if gadolinium-based contrast agents cannot be administered.
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Development of the brain's functional network architecture.

Issue 4 Vol 20 Published on 2010-12-01 PMID 20976563 PMCID PMC3811138
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DOI: https://doi.org/10.1007/s11065-010-9145-7
Authors: Alecia C Vogel In X Jonathan D Power In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.
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Prediction of individual brain maturity using fMRI.

Issue 5997 Vol 329 Published on 2010-09-01 PMID 20829489 PMCID PMC3135376
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DOI: https://doi.org/10.1126/science.1194144
Authors: Nico U F Dosenbach In X Binyam Nardos In X Alexander L Cohen In X Damien A Fair In X Jonathan D Power In X Jessica A Church In X Steven M Nelson In X Gagan S Wig In X Alecia C Vogel In X Christina N Lessov-Schlaggar In X Kelly Anne Barnes In X Joseph W Dubis In X Eric Feczko In X Rebecca S Coalson In X John R Pruett In X Deanna M Barch In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.
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Delighted to announce our latest publication 'Prediction of individual brain maturity using fMRI.' by Dosenbach et al:
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The development of human functional brain networks.

Issue 5 Vol 67 Published on 2010-09-01 PMID 20826306 PMCID PMC2941973
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DOI: https://doi.org/10.1016/j.neuron.2010.08.017
Authors: Jonathan D Power In X Damien A Fair In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Recent advances in MRI technology have enabled precise measurements of correlated activity throughout the brain, leading to the first comprehensive descriptions of functional brain networks in humans. This article reviews the growing literature on the development of functional networks, from infancy through adolescence, as measured by resting-state functional connectivity MRI. We note several limitations of traditional approaches to describing brain networks and describe a powerful framework for analyzing networks, called graph theory. We argue that characterization of the development of brain systems (e.g., the default mode network) should be comprehensive, considering not only relationships within a given system, but also how these relationships are situated within wider network contexts. We note that, despite substantial reorganization of functional connectivity, several large-scale network properties appear to be preserved across development, suggesting that functional brain networks, even in children, are organized in manners similar to other complex systems.
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The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

Issue 2 Vol 114 Published on 2010-08-01 PMID 19819000 PMCID PMC2888929
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DOI: https://doi.org/10.1016/j.bandl.2009.09.001
Authors: Damien A Fair In X Alexander H Choi In X Yannic B L Dosenbach In X Rebecca S Coalson In X Francis M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries.
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A parcellation scheme for human left lateral parietal cortex.

Issue 1 Vol 67 Published on 2010-07-01 PMID 20624599 PMCID PMC2913443
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DOI: https://doi.org/10.1016/j.neuron.2010.05.025
Authors: Steven M Nelson In X Alexander L Cohen In X Jonathan D Power In X Gagan S Wig In X Francis M Miezin In X Mark E Wheeler In X Katerina Velanova In X David I Donaldson In X Jeffrey S Phillips In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The parietal lobe has long been viewed as a collection of architectonic and functional subdivisions. Though much parietal research has focused on mechanisms of visuospatial attention and control-related processes, more recent functional neuroimaging studies of memory retrieval have reported greater activity in left lateral parietal cortex (LLPC) when items are correctly identified as previously studied ("old") versus unstudied ("new"). These studies have suggested functional divisions within LLPC that may provide distinct contributions toward recognition memory judgments. Here, we define regions within LLPC by developing a parcellation scheme that integrates data from resting-state functional connectivity MRI and functional MRI. This combined approach results in a 6-fold parcellation of LLPC based on the presence (or absence) of memory-retrieval-related activity, dissociations in the profile of task-evoked time courses, and membership in large-scale brain networks. This parcellation should serve as a roadmap for future investigations aimed at understanding LLPC function.
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Comprehensive analysis in 'A parcellation scheme for human left lateral parietal cortex.' reveals critical findings. Exceptional work by Nelson:
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Can sites prone to flow induced vascular complications in a-v fistulas be assessed using computational fluid dynamics?

Issue 10 Vol 43 Published on 2010-07-01 PMID 20382386 PMCID N/A
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DOI: https://doi.org/10.1016/j.jbiomech.2010.02.037
Authors: A K Niemann In X J Udesen In X S Thrysoe In X J V Nygaard In X E-T Fründ In X S E Petersen In X J M Hasenkam In X
Abstract: Arterio-venous fistulas (shunts between arteries and veins) are the preferred vascular access for hemodialysis. Despite their superior patency, compared with synthetic tubes and grafts, functional problems and inadequate flow rates are the common complications. Local flow conditions, in particular low and oscillating wall shear stresses (WSS), are central to vascular problems and a robust framework for analyzing flow conditions in vascular structures could provide an understanding of the mechanisms leading to vascular complications, such as stenoses, aneurisms, and thromboses. We hypothesize that a validated computational fluid dynamics (CFD) framework can be used to identify critical fistula configurations with elevated risk of complications. Therefore, the aim of the present study was to develop a CFD framework for analyzing fluid flow in complex vascular structures, such as arterio-venous fistulas validated by comparisons of in vitro volume flows with CFD results and flow fields from ultrasound scans with CFD simulations. Volume flows measured in vitro and CFD data differed quantitatively. However, good relative correlations exist between the data using logarithmic scales. Qualitatively, visual comparisons between ultrasound and CFD images showed good agreement between the two methods. In addition, WSS levels and the oscillatory shear index (OSI) were calculated and visualized on the model surface. The method was successfully validated and the method is deemed suitable for more thorough investigations into the field of vascular complications in a-v fistulas.
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Role of the anterior insula in task-level control and focal attention.

Open Access Issue 5-6 Vol 214 Published on 2010-06-01 PMID 20512372 PMCID PMC2886908
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DOI: https://doi.org/10.1007/s00429-010-0260-2
Authors: Steven M Nelson In X Nico U F Dosenbach In X Alexander L Cohen In X Mark E Wheeler In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: In humans, the anterior insula (aI) has been the topic of considerable research and ascribed a vast number of functional properties by way of neuroimaging and lesion studies. Here, we argue that the aI, at least in part, plays a role in domain-general attentional control and highlight studies (Dosenbach et al. 2006; Dosenbach et al. 2007) supporting this view. Additionally, we discuss a study (Ploran et al. 2007) that implicates aI in processes related to the capture of focal attention. Task-level control and focal attention may or may not reflect information processing supported by a single functional area (within the aI). Therefore, we apply a novel technique (Cohen et al. 2008) that utilizes resting state functional connectivity MRI (rs-fcMRI) to determine whether separable regions exist within the aI. rs-fcMRI mapping suggests that the ventral portion of the aI is distinguishable from more dorsal/anterior regions, which are themselves distinct from more posterior parts of the aI. When these regions are applied to functional MRI (fMRI) data, the ventral and dorsal/anterior regions support processes potentially related to both task-level control and focal attention, whereas the more posterior aI regions did not. These findings suggest that there exists some functional heterogeneity within aI that may subserve related but distinct types of higher-order cognitive processing.
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The "Task B problem" and other considerations in developmental functional neuroimaging.

Issue 6 Vol 31 Published on 2010-06-01 PMID 20496376 PMCID PMC3468298
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DOI: https://doi.org/10.1002/hbm.21036
Authors: Jessica A Church In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Functional neuroimaging provides a remarkable tool to allow us to study cognition across the lifespan and in special populations in a safe way. However, experimenters face a number of methodological issues, and these issues are particularly pertinent when imaging children. This brief article discusses assessing task performance, strategies for dealing with group performance differences, controlling for movement, statistical power, proper atlas registration, and data analysis strategies. In addition, there will be discussion of two other topics that have important implications for interpreting fMRI data: the question of whether functional neuroanatomical differences between adults and children are the consequence of putative developmental neurovascular differences, and the issue of interpreting negative blood oxygenation-level dependent (BOLD) signal change.
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MRI after implantation of a novel femoral closure device following intra-arterial catheterisation: implications for subsequent contrast-enhanced MR angiography.

Issue 5 Vol 20 Published on 2010-05-01 PMID 19936755 PMCID N/A
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DOI: https://doi.org/10.1007/s00330-009-1661-6
Authors: Oliver K Mohrs In X Steffen E Petersen In X Bernd Nowak In X Hans-Ulrich Kauczor In X Thomas Voigtlaender In X
Abstract:

Objective

To assess MRI safety aspects and artefacts of a novel femoral artery closure device during contrast-enhanced MR angiography in patients following intra-arterial catheterisation.

Methods

Ten consecutive patients underwent MRI within 24 h of coronary angiography and placement of a femoral artery closure device. We used a T2-weighted gradient-echo MRI sequence to measure the device-related artefact size in comparison with a phantom image, phase-contrast flow measurement proximal to, at the level of and distal to the device to quantify potential differences in flow velocity and contrast-enhanced 3D gradient-echo MR angiography to differentiate potential femoral artery stenosis from device-related artefacts.

Results

The mean size of the oval-shaped artefact was 8.4 x 6.6 mm (+/-1.0 x 0.8 mm) and was almost identical to the maximum artefact size of the phantom measurement (8.3 x 5.7 mm). Device placement did not result in an increased peak velocity (proximal 69 +/- 23 cm/s, at the level of 64 +/- 11 cm/s and distal to the device 63 +/- 12 cm/s, p = 0.67). The mean artefact penetration into the vessel lumen was 0.5 +/- 0.5 mm (percentage vessel narrowing 7.0 +/- 6%; range 0-16%).

Conclusion

The MR conditional StarClose femoral artery closure device was used safely within 24 h of deployment at 1.5 T. Despite clip-related artefacts MR angiography will allow for easy differentiation of clip-related artefacts from high-grade atherosclerotic stenosis.
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Letter by yilmaz et Al regarding article, "analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy".

Issue 2 Vol 3 Published on 2010-04-01 PMID 20407095 PMCID N/A
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DOI: https://doi.org/10.1161/circgenetics.109.933614
Authors: Ali Yilmaz In X Joseph Suttie In X Steffen E Petersen In X
Abstract: No Abstract Available
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So excited to see our paper, 'Letter by yilmaz et Al regarding article, "analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy".', in print! A great team effort with Yilmaz et al.:
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Managing superior vena cava syndrome as a complication of pacemaker implantation: a pooled analysis of clinical practice.

Issue 4 Vol 33 Published on 2010-04-01 PMID 20051021 PMCID N/A
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DOI: https://doi.org/10.1111/j.1540-8159.2009.02613.x
Authors: Robert F Riley In X Steffen E Petersen In X John D Ferguson In X Yaver Bashir In X
Abstract:

Background

Superior vena cava syndrome (SVCS) is a rare complication of pacemaker implantation. Numerous methods have been employed to treat this condition, ranging from anticoagulation and thrombolysis to surgical interventions and stenting. However, thus far only small case series have been reported and there is no currently accepted standard of care.

Methods

Our group preformed a PubMed literature search to identify cases of symptomatic SVCS that developed following implantation of permanent pacemakers or implanatable cardioverter defibrillators and were treated with one of five different modalities: anticoagulation, thrombolysis, venoplasty, stenting, and surgical reconstuction. Duration of follow-up and incidence of recurrence of symptoms were the main end-points.

Results

One hundred and four eligible cases from 74 different publications were identified, in which SVCS presented at a median of 48 (range 0-396) months after device implantation. We found that over the last 40 years, conservative treatments have been replaced by surgical reconstruction, and most recently by stenting, as the most common therapeutic modality employed. Anticoagulation, thrombolysis, and venoplasty alone were all associated with high recurrence rates. Surgery and stenting were more successful: recurrence rates were 12% and 5% over a median follow-up of 16 (range: 2-179) and 9.5 (range: 2-60) months, respectively.

Conclusions

Currently, transvenous stenting is the most common treatment used for pacemaker-related SVCS, usually with conservation of the implanted leads. Both surgery and stenting appear to be effective treatments, with low incidences of recurrent SVCS over the first 12 months, but there is unfortunately a paucity of data on long-term outcomes. (PACE 2010; 420-425).
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Toward discovery science of human brain function.

Issue 10 Vol 107 Published on 2010-03-01 PMID 20176931 PMCID PMC2842060
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DOI: https://doi.org/10.1073/pnas.0911855107
Authors: Bharat B Biswal In X Maarten Mennes In X Xi-Nian Zuo In X Suril Gohel In X Clare Kelly In X Steve M Smith In X Christian F Beckmann In X Jonathan S Adelstein In X Randy L Buckner In X Stan Colcombe In X Anne-Marie Dogonowski In X Monique Ernst In X Damien Fair In X Michelle Hampson In X Matthew J Hoptman In X James S Hyde In X Vesa J Kiviniemi In X Rolf Kötter In X Shi-Jiang Li In X Ching-Po Lin In X Mark J Lowe In X Clare Mackay In X David J Madden In X Kristoffer H Madsen In X Daniel S Margulies In X Helen S Mayberg In X Katie McMahon In X Christopher S Monk In X Stewart H Mostofsky In X Bonnie J Nagel In X James J Pekar In X Scott J Peltier In X Steven E Petersen In X Valentin Riedl In X Serge A R B Rombouts In X Bart Rypma In X Bradley L Schlaggar In X Sein Schmidt In X Rachael D Seidler In X Greg J Siegle In X Christian Sorg In X Gao-Jun Teng In X Juha Veijola In X Arno Villringer In X Martin Walter In X Lihong Wang In X Xu-Chu Weng In X Susan Whitfield-Gabrieli In X Peter Williamson In X Christian Windischberger In X Yu-Feng Zang In X Hong-Ying Zhang In X F Xavier Castellanos In X Michael P Milham In X
Abstract: Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
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Remember the source: dissociating frontal and parietal contributions to episodic memory.

Issue 2 Vol 22 Published on 2010-02-01 PMID 19400677 PMCID N/A
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DOI: https://doi.org/10.1162/jocn.2009.21242
Authors: David I Donaldson In X Mark E Wheeler In X Steve E Petersen In X
Abstract: Event-related fMRI studies reveal that episodic memory retrieval modulates lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and anterior PFC. These regions respond more for recognized old than correctly rejected new words, suggesting a neural correlate of retrieval success. Despite significant efforts examining retrieval success regions, their role in retrieval remains largely unknown. Here we asked the question, to what degree are the regions performing memory-specific operations? And if so, are they all equally sensitive to successful retrieval, or are other factors such as error detection also implicated? We investigated this question by testing whether activity in retrieval success regions was associated with task-specific contingencies (i.e., perceived targetness) or mnemonic relevance (e.g., retrieval of source context). To do this, we used a source memory task that required discrimination between remembered targets and remembered nontargets. For a given region, the modulation of neural activity by a situational factor such as target status would suggest a more domain-general role; similarly, modulations of activity linked to error detection would suggest a role in monitoring and control rather than the accumulation of evidence from memory per se. We found that parietal retrieval success regions exhibited greater activity for items receiving correct than incorrect source responses, whereas frontal retrieval success regions were most active on error trials, suggesting that posterior regions signal successful retrieval whereas frontal regions monitor retrieval outcome. In addition, perceived targetness failed to modulate fMRI activity in any retrieval success region, suggesting that these regions are retrieval specific. We discuss the different functions that these regions may support and propose an accumulator model that captures the different pattern of responses seen in frontal and parietal retrieval success regions.
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Identifying Basal Ganglia divisions in individuals using resting-state functional connectivity MRI.

Open Access Issue N/A Vol 4 Published on 2010-01-01 PMID 20589235 PMCID PMC2892946
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Keywords: Striatum, Graph theory, Functional Connectivity, Cortico-basal Ganglia Loops, Connectome
DOI: https://doi.org/10.3389/fnsys.2010.00018
Authors: Kelly Anne Barnes In X Alexander L Cohen In X Jonathan D Power In X Steven M Nelson In X Yannic B L Dosenbach In X Francis M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Studies in non-human primates and humans reveal that discrete regions (henceforth, "divisions") in the basal ganglia are intricately interconnected with regions in the cerebral cortex. However, divisions within basal ganglia nuclei (e.g., within the caudate) are difficult to identify using structural MRI. Resting-state functional connectivity MRI (rs-fcMRI) can be used to identify putative cerebral cortical functional areas in humans (Cohen et al., 2008). Here, we determine whether rs-fcMRI can be used to identify divisions in individual human adult basal ganglia. Putative basal ganglia divisions were generated by assigning basal ganglia voxels to groups based on the similarity of whole-brain functional connectivity correlation maps using modularity optimization, a network analysis tool. We assessed the validity of this approach by examining the spatial contiguity and location of putative divisions and whether divisions' correlation maps were consistent with previously reported patterns of anatomical and functional connectivity. Spatially constrained divisions consistent with the dorsal caudate, ventral striatum, and dorsal caudal putamen could be identified in each subject. Further, correlation maps associated with putative divisions were consistent with their presumed connectivity. These findings suggest that, as in the cerebral cortex, subcortical divisions can be identified in individuals using rs-fcMRI. Developing and validating these methods should improve the study of brain structure and function, both typical and atypical, by allowing for more precise comparison across individuals.
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Exceptional publication 'Identifying Basal Ganglia divisions in individuals using resting-state functional connectivity MRI.' demonstrates innovative approaches by Barnes:
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Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Issue 1 Vol 17 Published on 2010-01-01 PMID 20141602 PMCID N/A
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DOI: https://doi.org/10.1111/j.1549-8719.2010.00002.x
Authors: Nico Abegunewardene In X Kai-Helge Schmidt In X Markus Vosseler In X Michael Dreher In X Tandis Keller In X Nico Hoffmann In X Kerstin Veit In X Steffen E Petersen In X Hans-Anton Lehr In X Laura M Schreiber In X Tommaso Gori In X Georg Horstick In X Thomas Münzel In X
Abstract:

Background

This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia.

Methods and results

Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05).

Conclusions

Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.
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(31)P cardiac magnetic resonance spectroscopy during leg exercise at 3 Tesla.

Issue 8 Vol 25 Published on 2009-12-01 PMID 19697152 PMCID N/A
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DOI: https://doi.org/10.1007/s10554-009-9492-8
Authors: Lucy E Hudsmith In X Damian J Tyler In X Yaso Emmanuel In X Steffen E Petersen In X Jane M Francis In X Hugh Watkins In X Kieran Clarke In X Matthew D Robson In X Stefan Neubauer In X
Abstract: Investigation of phosphorus ((31)P) magnetic resonance spectroscopy under stress conditions provides a non-invasive tool to examine alterations in cardiac high-energy phosphate metabolism that may not be evident at rest. Our aim was to establish cardiac (31)P MR spectroscopy during leg exercise at 3T. The increased field strength should provide a higher signal to noise ratio than at lower field strengths. Furthermore, relatively high temporal resolution at a sufficiently fine spatial resolution should be feasible. (31)P MR spectra were obtained with a 3D acquisition weighted chemical shift imaging sequence in 20 healthy volunteers at rest, during dynamic physiological leg exercise and after recovery at 3T. Haemodynamic measurements were made throughout and the rate pressure product calculated. With exercise, the mean heart rate increased by 73%, achieving a mean increase in rate pressure product of 115%. The corrected PCr/ATP ratio for subjects at rest was 2.02 +/- 0.43, exercise 2.14 +/- 0.67 (P = 0.54 vs. rest) and at recovery 2.03 +/- 0.52 (P = 0.91 vs. rest, P = 0.62 vs. exercise). A cardiac (31)P MR spectroscopy physiological exercise-recovery protocol is feasible at 3T. There was no significant change in high-energy cardiac phosphate metabolite concentrations in healthy volunteers at rest, during physiological leg exercise or during recovery. When applied to patients with heart disease, this protocol should provide insights into physiological and pathological cardiac metabolism.
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Usefulness of MRI to differentiate between temporary and long-term coronary artery occlusion in a minimally invasive model of experimental myocardial infarction.

Issue 5 Vol 32 Published on 2009-09-01 PMID 19472001 PMCID N/A
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DOI: https://doi.org/10.1007/s00270-009-9596-5
Authors: Nico Abegunewardene In X Markus Vosseler In X Tommaso Gori In X Nico Hoffmann In X Kai-Helge Schmidt In X Dietmar Becker In X Karl-Friedrich Kreitner In X Steffen E Petersen In X Laura M Schreiber In X Georg Horstick In X Thomas Münzel In X
Abstract: The surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 +/- 4.4%; p = 0.008) and group 2 (9.4 +/- 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 +/- 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 +/- 0.3, 5.9 +/- 0.7, and 6.1 +/- 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 +/- 2.1%) compared to group 1 (5.3 +/- 5.4%; p = 0.003) and group 2 (9.7 +/- 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.
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Beneficial cardiovascular effects of bariatric surgical and dietary weight loss in obesity.

Issue 8 Vol 54 Published on 2009-08-01 PMID 19679250 PMCID N/A
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DOI: https://doi.org/10.1016/j.jacc.2009.02.086
Authors: Oliver J Rider In X Jane M Francis In X Mohammed K Ali In X Steffen E Petersen In X Monique Robinson In X Matthew D Robson In X James P Byrne In X Kieran Clarke In X Stefan Neubauer In X
Abstract:

Objectives

We hypothesized that, in obese persons without comorbidities, cardiovascular responses to excess weight are reversible during weight loss by either bariatric surgery or diet.

Background

Obesity is associated with cardiac hypertrophy, diastolic dysfunction, and increased aortic stiffness, which are independent predictors of cardiovascular risk.

Methods

Thirty-seven obese (body mass index 40 +/- 8 kg/m(2)) and 20 normal-weight subjects (body mass index 21 +/- 2 kg/m(2)) without identifiable cardiac risk factors underwent cardiac magnetic resonance imaging for the assessment of the left and right ventricles and of indexes of aortic function. Thirty of the obese subjects underwent repeat imaging after 1 year of significant weight loss, achieved in 17 subjects by diet and in 13 subjects by bariatric surgery. Seven obese subjects underwent repeat imaging after 1 year of continued obesity.

Results

Left and right ventricular masses were significantly increased, left ventricular diastolic function impaired, and aortic distensibility reduced in the obese. Both diet and bariatric surgery led to comparable, significant decreases in left and right ventricular masses, end-diastolic volume, and diastolic dysfunction, and an increase in aortic distensibility at all levels of the aorta, most pronounced distally (e.g., distal descending aorta 5.1 +/- 1.8 mm Hg(-1) x 10(-3) before weight loss and 6.8 +/- 2.5 mm Hg(-1) x 10(-3) after weight loss; p < 0.001). No improvements were observed in continued obesity.

Conclusions

Irrespective of method, 1 year of weight loss leads to partial regression of cardiac hypertrophy and to reversal of both diastolic dysfunction and aortic distensibility impairment. These findings provide a potential mechanism for the reduction in mortality seen with weight loss.
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Resting-state functional connectivity in the human brain revealed with diffuse optical tomography.

Issue 1 Vol 47 Published on 2009-08-01 PMID 19344773 PMCID PMC2699418
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DOI: https://doi.org/10.1016/j.neuroimage.2009.03.058
Authors: Brian R White In X Abraham Z Snyder In X Alexander L Cohen In X Steven E Petersen In X Marcus E Raichle In X Bradley L Schlaggar In X Joseph P Culver In X
Abstract: Mapping resting-state networks allows insight into the brain's functional architecture and physiology and has rapidly become important in contemporary neuroscience research. Diffuse optical tomography (DOT) is an emerging functional neuroimaging technique with the advantages, relative to functional magnetic resonance imaging (fMRI), of portability and the ability to simultaneously measure both oxy- and deoxyhemoglobin. Previous optical studies have evaluated the temporal features of spontaneous resting brain signals. Herein, we develop techniques for spatially mapping functional connectivity with DOT (fc-DOT). Simultaneous imaging over the motor and visual cortices yielded robust correlation maps reproducing the expected functional neural architecture. The localization of the maps was confirmed with task-response studies and with subject-matched fc-MRI. These fc-DOT methods provide a task-less approach to mapping brain function in populations that were previously difficult to research. Our advances may permit new studies of early childhood development and of unconscious patients. In addition, the comprehensive hemoglobin contrasts of fc-DOT enable innovative studies of the biophysical origin of the functional connectivity signal.
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Functional brain networks develop from a "local to distributed" organization.

Open Access Issue 5 Vol 5 Published on 2009-05-01 PMID 19412534 PMCID PMC2671306
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DOI: https://doi.org/10.1371/journal.pcbi.1000381
Authors: Damien A Fair In X Alexander L Cohen In X Jonathan D Power In X Nico U F Dosenbach In X Jessica A Church In X Francis M Miezin In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward 'segregation' (a general decrease in correlation strength) between regions close in anatomical space and 'integration' (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more "distributed" architecture in young adults. We argue that this "local to distributed" developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing "small-world"-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways.
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Determinants of left ventricular mass in obesity; a cardiovascular magnetic resonance study.

Open Access Issue N/A Vol 11 Published on 2009-04-01 PMID 19393079 PMCID PMC2680851
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DOI: https://doi.org/10.1186/1532-429x-11-9
Authors: Oliver J Rider In X Jane M Francis In X Mohammed K Ali In X James Byrne In X Kieran Clarke In X Stefan Neubauer In X Steffen E Petersen In X
Abstract:

Background

Obesity is linked to increased left ventricular mass, an independent predictor of mortality. As a result of this, understanding the determinants of left ventricular mass in the setting of obesity has both therapeutic and prognostic implications. Using cardiovascular magnetic resonance our goal was to elucidate the main predictors of left ventricular mass in severely obese subjects free of additional cardiovascular risk factors.

Methods

38 obese (BMI 37.8 +/- 6.9 kg/m2) and 16 normal weight controls subjects, (BMI 21.7 +/- 1.8 kg/m2), all without cardiovascular risk factors, underwent cardiovascular magnetic resonance imaging to assess left ventricular mass, left ventricular volumes and visceral fat mass. Left ventricular mass was then compared to serum and anthropometric markers of obesity linked to left ventricular mass, i.e. height, age, blood pressure, total fat mass, visceral fat mass, lean mass, serum leptin and fasting insulin level.

Results

As expected, obesity was associated with significantly increased left ventricular mass (126 +/- 27 vs 90 +/- 20 g; p < 0.001). Stepwise multiple regression analysis showed that over 75% of the cross sectional variation in left ventricular mass can be explained by lean body mass (beta = 0.51, p < 0.001), LV stroke volume (beta = 0.31 p = 0.001) and abdominal visceral fat mass (beta = 0.20, p = 0.02), all of which showed highly significant independent associations with left ventricular mass (overall R2 = 0.77).

Conclusion

The left ventricular hypertrophic response to obesity in the absence of additional cardiovascular risk factors is mainly attributable to increases in lean body mass, LV stroke volume and visceral fat mass. In view of the well documented link between obesity, left ventricular hypertrophy and mortality, these findings have potentially important prognostic and therapeutic implications for primary and secondary prevention.
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Lack of generalizability of sex differences in the fMRI BOLD activity associated with language processing in adults.

Issue 3 Vol 45 Published on 2009-04-01 PMID 19162200 PMCID PMC2656426
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DOI: https://doi.org/10.1016/j.neuroimage.2008.12.034
Authors: S K Z Ihnen In X Jessica A Church In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: A lack of consensus exists as to whether there are sex differences in the fMRI BOLD signal correlates of language processing in the human brain. Here, whole-brain fMRI was used to examine the neural activity of 46 adults performing one of two sets of language tasks. Conservative quantitative and qualitative criteria identified a handful of statistically significant regions of "sex difference" within each task separately. When each of the two sets of regions was investigated in the group of subjects performing the other task set, however, most of the identified "sex differences" failed to generalize. Identical analyses of the same subjects divided into sex-matched pseudorandom control groups for each task set separately revealed that it is possible to observe a similar number of statistically significant regions of "group difference" in the task-associated BOLD signal, even when the groups do not differ on any of the measured behavioral parameters, or any obvious demographic characteristic. Together, these results suggest that one should be cautious when interpreting studies that purport to have identified regions of difference between groups, whether those groups are divided by sex or by any other criterion. In particular, generalization or replication of a result in independent data sets is necessary for establishing conclusive support for any hypothesis about differences in brain function between groups.
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Impaired left ventricular energy metabolism in hypertrophic cardiomyopathy is not due to fibrosis.

Issue 6 Vol 95 Published on 2009-03-01 PMID 19252011 PMCID N/A
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DOI: #
Authors: S E Petersen In X H Watkins In X S Neubauer In X
Abstract: No Abstract Available
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Mapping the human brain at rest with diffuse optical tomography.

Issue N/A Vol 2009 Published on 2009-01-01 PMID 19964102 PMCID PMC4120748
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DOI: https://doi.org/10.1109/iembs.2009.5333199
Authors: Brian R White In X Abraham Z Snyder In X Alexander L Cohen In X Steven E Petersen In X Marcus E Raichle In X Bradley L Schlaggar In X Joseph P Culver In X
Abstract: Diffuse optical tomography (DOT) is a portable functional neuroimaging technique that is able to simultaneously measure both oxy- and deoxyhemoglobin responses to brain activity. Herein, we demonstrate a technique for mapping functional connections in the brain by measuring the spatial distribution of temporal correlations in resting brain activity. Simultaneous DOT imaging over the motor and visual cortices yielded robust correlation maps reproducing the expected functional neural architecture. These functional connectivity methods will have utility in certain populations, such as those who are unconscious or very young, who have difficulty performing the behaviors required in traditional task-based functional neuroimaging paradigms.
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Task control signals in pediatric tourette syndrome show evidence of immature and anomalous functional activity.

Open Access Issue N/A Vol 3 Published on 2009-01-01 PMID 19949483 PMCID PMC2784679
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Keywords: Development, Control, fMRI, Tourette syndrome, Adolescence
DOI: https://doi.org/10.3389/neuro.09.038.2009
Authors: Jessica A Church In X Kristin K Wenger In X Nico U F Dosenbach In X Francis M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with "anomalous" correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development ("anomalous"). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS.
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Area at risk and viability after myocardial ischemia and reperfusion can be determined by contrast-enhanced cardiac magnetic resonance imaging.

Issue 1 Vol 43 Published on 2009-01-01 PMID 19365131 PMCID N/A
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DOI: https://doi.org/10.1159/000211716
Authors: M Vosseler In X N Abegunewardene In X N Hoffmann In X S E Petersen In X D Becker In X D Cleppien In X P Kunz In X K-F Kreitner In X M Lauterbach In X B Bierbach In X C Düber In X T Gori In X T Munzel In X L M Schreiber In X G Horstick In X
Abstract:

Background/aims

Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia.

Methods

Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining.

Results

The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14-15%) while good agreement was present in group B.

Conclusion

The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.
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Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity.

Open Access Issue Pt 1 Vol 132 Published on 2009-01-01 PMID 18952678 PMCID PMC2638693
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DOI: https://doi.org/10.1093/brain/awn223
Authors: Jessica A Church In X Damien A Fair In X Nico U F Dosenbach In X Alexander L Cohen In X Francis M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called 'tics'. Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously defined putative control regions in 33 adolescents with TS. We were particularly interested in the effect of TS on two of the brain's task control networks-a fronto-parietal network likely involved in more rapid, adaptive online control, and a cingulo-opercular network apparently important for set-maintenance. To examine the relative maturity of connections in the Tourette subjects, functional connections that changed significantly over typical development were examined. Age curves were created for each functional connection charting correlation coefficients over age for 210 healthy people aged 7-31 years, and the TS group correlation coefficients were compared to these curves. Many of these connections were significantly less 'mature' than expected in the TS group. This immaturity was true not only for functional connections that grow stronger with age, but also for those that diminish in strength with age. To explore other differences between Tourette and typically developing subjects further, we performed a second analysis in which the TS group was directly compared to an age-matched, movement-matched group of typically developing, unaffected adolescents. A number of functional connections were found to differ between the two groups. For these identified connections, a large number of connectional differences were found where the TS group value was out of range compared to typical developmental age curves. These anomalous connections were primarily found in the fronto-parietal network, thought to be important for online adaptive control. These results suggest that in adolescents with TS, immature functional connectivity is widespread, with additional, more profound deviation of connectivity in regions related to adaptive online control.
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Dissociating early and late error signals in perceptual recognition.

Issue 12 Vol 20 Published on 2008-12-01 PMID 18457507 PMCID N/A
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DOI: https://doi.org/10.1162/jocn.2008.20155
Authors: Mark E Wheeler In X Steven E Petersen In X Steven M Nelson In X Elisabeth J Ploran In X Katerina Velanova In X
Abstract: Decisions about object identity follow a period in which evidence is gathered and analyzed. Evidence can consist of both task-relevant external stimuli and internally generated goals and expectations. How the various pieces of information are gathered and filtered into meaningful evidence by the nervous system is largely unknown. Although object recognition is often highly efficient and accurate, errors are common. Errors may be related to faulty evidence gathering arising from early misinterpretations of incoming stimulus information. In addition, errors in task performance are known to elicit late corrective performance monitoring mechanisms that can optimize or otherwise adjust future behavior. In this study, we used functional magnetic resonance imaging (fMRI) in an extended trial paradigm of object recognition to study whether we could identify performance-based signal modulations prior to and following the moment of recognition. The rationale driving the current report is that early modulations in fMRI activity may reflect faulty evidence gathering, whereas late modulations may reflect the presence of performance monitoring mechanisms. We tested this possibility by comparing fMRI activity on correct and error trials in regions of interest (ROIs) that were selected a priori. We found pre- and postrecognition accuracy-dependent modulation in different sets of a priori ROIs, suggesting the presence of dissociable error signals.
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Medial temporal lobe BOLD activity at rest predicts individual differences in memory ability in healthy young adults.

Issue 47 Vol 105 Published on 2008-11-01 PMID 19001272 PMCID PMC2582045
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DOI: https://doi.org/10.1073/pnas.0804546105
Authors: Gagan S Wig In X Scott T Grafton In X Kathryn E Demos In X George L Wolford In X Steven E Petersen In X William M Kelley In X
Abstract: Human beings differ in their ability to form and retrieve lasting long-term memories. To explore the source of these individual differences, we used functional magnetic resonance imaging to measure blood-oxygen-level-dependent (BOLD) activity in healthy young adults (n = 50) during periods of resting fixation that were interleaved with periods of simple cognitive tasks. We report that medial temporal lobe BOLD activity during periods of rest predicts individual differences in memory ability. Specifically, individuals who exhibited greater magnitudes of task-induced deactivations in medial temporal lobe BOLD signal (as compared to periods of rest) demonstrated superior memory during offline testing. This relationship was independent of differences in general cognitive function and persisted across different control tasks (i.e., number judgment versus checkerboard detection) and experimental designs (i.e., blocked versus event-related). These results offer a neurophysiological basis for the variability in mnemonic ability that is present amongst healthy young adults and may help to guide strategies aimed at early detection and intervention of neurological and mnemonic impairment.
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A developmental fMRI study of reading and repetition reveals changes in phonological and visual mechanisms over age.

Issue 9 Vol 18 Published on 2008-09-01 PMID 18245043 PMCID PMC2517103
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DOI: https://doi.org/10.1093/cercor/bhm228
Authors: Jessica A Church In X Rebecca S Coalson In X Heather M Lugar In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: In this study of reading development, children (ages 7-10) and adults (ages 18-32) performed overt single-word reading and aural repetition tasks on high-frequency word stimuli during functional magnetic resonance imaging. Most regions showed similar activity across age groups. These widespread regions of similarity indicate that children and adults use largely overlapping mechanisms when processing high-frequency words. Significant task-related differences included greater activity in occipital cortex for the read task, and greater activity in temporal cortex for the repeat task; activity levels in these regions were similar for adults and children. However, age group differences were found in several posterior regions, including a set of regions implicated in adult reading: the left supramarginal gyrus, the left angular gyrus, and bilateral anterior extrastriate cortex. The angular and supramarginal gyrus regions, hypothesized to play a role in phonology, showed decreased activity in adults relative to children for high-frequency words. The extrastriate regions had significant activity for both the visual read task and auditory repeat task in children, but just for the read task in adults, showing significant task and age interactions. These results are consistent with decreasing reliance on phonological processing, and increasing tuning of visual mechanisms, with age.
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First experiences with contrast-enhanced first-pass MR perfusion imaging in patients with primary, benign cardiac masses and tumour-like lesions.

Issue 8 Vol 18 Published on 2008-08-01 PMID 18343927 PMCID N/A
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DOI: https://doi.org/10.1007/s00330-008-0910-4
Authors: Oliver K Mohrs In X Thomas Voigtlaender In X Steffen E Petersen In X Matthias Zander In X Thomas Schulze In X Anselm Pottmeyer In X Hans-Ulrich Kauczor In X
Abstract: The aim of this study was to evaluate the diagnostic value of contrast-enhanced first-pass perfusion MRI in patients with suspected cardiac masses and tumour-like lesions. Twenty patients underwent contrast-enhanced first-pass saturation-recovery steady-state-free-precession perfusion MRI in addition to clinical MRI. Eleven diagnostic parameters were analysed blinded in consensus by three observers: localisation (paracardiac/mural/intracavitary), malignancy (benign/malignant) and first-pass enhancement pattern (homogeneous/heterogeneous as well as non-perfused/hypoperfused/iso-perfused/ hyperperfused). The results were compared to combined references comprising histology, cytology, medical and surgical reports, echocardiography, chest X-ray, coronary angiography and regular MRI. Also, we analysed if additional first-pass perfusion confirmed, changed or reduced the number of differential diagnoses compared to clinical MRI. All cardiac masses or tumour-like lesions were correctly localised and scored as benign lesions. For homogeneous perfused lesions the sensitivity, specificity, positive and negative predictive value was 94/100/100/67%, 100/94/67/100% for heterogeneous perfused lesions, 92/100/100/88% for non-perfused, 100/94/75/100 for hypoperfused, 100/100/100/100% for hyperperfused and for isoperfused lesions. In 17/2/1 cases perfusion MRI confirmed, reduced or increased the number of potential differentials. First-pass perfusion MRI provides valuable information in patients with benign cardiac masses or tumour-like lesions. Further experience is needed to underline these preliminary observations.
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Athletes with repolarization abnormalities.

Issue 21 Vol 358 Published on 2008-05-01 PMID 18504831 PMCID N/A
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DOI: #
Authors: Jayanth R Arnold In X Theodoros D Karamitsos In X Steffen E Petersen In X
Abstract: No Abstract Available
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Defining functional areas in individual human brains using resting functional connectivity MRI.

Issue 1 Vol 41 Published on 2008-05-01 PMID 18367410 PMCID PMC2705206
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DOI: https://doi.org/10.1016/j.neuroimage.2008.01.066
Authors: Alexander L Cohen In X Damien A Fair In X Nico U F Dosenbach In X Francis M Miezin In X Donna Dierker In X David C Van Essen In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The cerebral cortex is anatomically organized at many physical scales starting at the level of single neurons and extending up to functional systems. Current functional magnetic resonance imaging (fMRI) studies often focus at the level of areas, networks, and systems. Except in restricted domains, (e.g., topographically-organized sensory regions), it is difficult to determine area boundaries in the human brain using fMRI. The ability to delineate functional areas non-invasively would enhance the quality of many experimental analyses allowing more accurate across-subject comparisons of independently identified functional areas. Correlations in spontaneous BOLD activity, often referred to as resting state functional connectivity (rs-fcMRI), are especially promising as a way to accurately localize differences in patterns of activity across large expanses of cortex. In the current report, we applied a novel set of image analysis tools to explore the utility of rs-fcMRI for defining wide-ranging functional area boundaries. We find that rs-fcMRI patterns show sharp transitions in correlation patterns and that these putative areal boundaries can be reliably detected in individual subjects as well as in group data. Additionally, combining surface-based analysis techniques with image processing algorithms allows automated mapping of putative areal boundaries across large expanses of cortex without the need for prior information about a region's function or topography. Our approach reliably produces maps of bounded regions appropriate in size and number for putative functional areas. These findings will hopefully stimulate further methodological refinements and validations.
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Early changes in arterial structure and function following statin initiation: quantification by magnetic resonance imaging.

Open Access Issue 2 Vol 197 Published on 2008-04-01 PMID 17977546 PMCID PMC2292239
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DOI: https://doi.org/10.1016/j.atherosclerosis.2007.09.001
Authors: Justin M S Lee In X Frank Wiesmann In X Cheerag Shirodaria In X Paul Leeson In X Steffen E Petersen In X Jane M Francis In X Clare E Jackson In X Matthew D Robson In X Stefan Neubauer In X Keith M Channon In X Robin P Choudhury In X
Abstract: Effective LDL-cholesterol (LDL-C) reduction improves vascular function and can bring about regression of atherosclerosis. Alterations in endothelial function can occur rapidly, but changes in atherosclerosis are generally considered to occur more slowly. Vascular magnetic resonance imaging (MRI) is a powerful technique for accurate non-invasive assessment of central and peripheral arteries at multiple anatomical sites. We report the changes in atherosclerosis burden and arterial function in response to open label statin treatment, in 24 statin-naïve newly diagnosed stable coronary artery disease patients. Patients underwent MRI before, and 3 and 12 months after commencing treatment. Mean LDL-C fell by 37% to 70.8 mg/dL (P<0.01). The plaque index (normalised vessel wall area) showed reductions in the aorta (2.3%, P<0.05) and carotid (3.1%, P<0.05) arteries at 3 months. Early reductions in atherosclerosis of aorta and carotid observed at 3 months were significantly correlated with later change at 12 months (R(2)=0.50, P<0.001; R(2)=0.22, P<0.05, respectively). Improvements in aortic distensibility and brachial endothelial function that were apparent after 3 months treatment were sustained at the 12-month time point.
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The maturing architecture of the brain's default network.

Issue 10 Vol 105 Published on 2008-03-01 PMID 18322013 PMCID PMC2268790
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DOI: https://doi.org/10.1073/pnas.0800376105
Authors: Damien A Fair In X Alexander L Cohen In X Nico U F Dosenbach In X Jessica A Church In X Francis M Miezin In X Deanna M Barch In X Marcus E Raichle In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: In recent years, the brain's "default network," a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a "default mode" of brain function. In early studies, investigators suggested that, the brain's default mode supports "self-referential" or "introspective" mental activity. Subsequently, regions of the default network have been more specifically related to the "internal narrative," the "autobiographical self," "stimulus independent thought," "mentalizing," and most recently "self-projection." However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7-9 years old); over development, these regions integrate into a cohesive, interconnected network.
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A dual-networks architecture of top-down control.

Issue 3 Vol 12 Published on 2008-03-01 PMID 18262825 PMCID PMC3632449
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DOI: https://doi.org/10.1016/j.tics.2008.01.001
Authors: Nico U F Dosenbach In X Damien A Fair In X Alexander L Cohen In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Complex systems ensure resilience through multiple controllers acting at rapid and slower timescales. The need for efficient information flow through complex systems encourages small-world network structures. On the basis of these principles, a group of regions associated with top-down control was examined. Functional magnetic resonance imaging showed that each region had a specific combination of control signals; resting-state functional connectivity grouped the regions into distinct 'fronto-parietal' and 'cingulo-opercular' components. The fronto-parietal component seems to initiate and adjust control; the cingulo-opercular component provides stable 'set-maintenance' over entire task epochs. Graph analysis showed dense local connections within components and weaker 'long-range' connections between components, suggesting a small-world architecture. The control systems of the brain seem to embody the principles of complex systems, encouraging resilient performance.
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Redefining cardiomyopathies: the role of cardiovascular magnetic resonance imaging.

Issue 24 Vol 28 Published on 2007-12-01 PMID 17965010 PMCID N/A
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DOI: https://doi.org/10.1093/eurheartj/ehm496
Authors: Theodoros D Karamitsos In X Jayanth R Arnold In X Stefan Neubauer In X Steffen E Petersen In X
Abstract: No Abstract Available
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Evidence accumulation and the moment of recognition: dissociating perceptual recognition processes using fMRI.

Issue 44 Vol 27 Published on 2007-10-01 PMID 17978031 PMCID PMC6673371
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DOI: https://doi.org/10.1523/jneurosci.3522-07.2007
Authors: Elisabeth J Ploran In X Steven M Nelson In X Katerina Velanova In X David I Donaldson In X Steven E Petersen In X Mark E Wheeler In X
Abstract: Decision making can be conceptualized as the culmination of an integrative process in which evidence supporting different response options accumulates gradually over time. We used functional magnetic resonance imaging to investigate brain activity leading up to and during decisions about perceptual object identity. Pictures were revealed gradually and subjects signaled the time of recognition (T(R)) with a button press. We examined the time course of T(R)-dependent activity to determine how brain regions tracked the timing of recognition. In several occipital regions, activity increased primarily as stimulus information increased, suggesting a role in lower-level sensory processing. In inferior temporal, frontal, and parietal regions, a gradual buildup in activity peaking in correspondence with T(R) suggested that these regions participated in the accumulation of evidence supporting object identity. In medial frontal cortex, anterior insula/frontal operculum, and thalamus, activity remained near baseline until T(R), suggesting a relation to the moment of recognition or the decision itself. The findings dissociate neural processes that function in concert during perceptual recognition decisions.
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Effects of steady state free precession parameters on cardiac mass, function, and volumes.

Issue 5 Vol 23 Published on 2007-10-01 PMID 17164984 PMCID N/A
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DOI: https://doi.org/10.1007/s10554-006-9191-7
Authors: Maureen C Hogan In X Steffen E Petersen In X Lucy E Hudsmith In X Jane M Francis In X Stefan Neubauer In X Matthew D Robson In X
Abstract:

Purpose

We aimed to investigate comparability of LV volumes, function, and mass acquired with three steady-state free precession (SSFP) pulse sequences, simulating typical vendor and protocol specific differences in data acquisition.

Methods

Twenty-one healthy subjects (11 male and 10 female; age range 23-49) underwent cardiac magnetic resonance (CMR) imaging at 1.5 Tesla (T). A complete stack of short-axis views covering the entire left ventricle (LV) were acquired for each of the three SSFP sequences, differing in the interslice gap and slice thickness (7 mm with no gap (7/0 mm); 7 mm with a 3 mm gap (7/3 mm) and 6 mm with a 4 mm gap (6/4 mm)) with slight variations in acquisition parameters. For each sequence, the LV volumes, function, and mass were determined. Intra- and inter-observer variability and inter-study reproducibility were assessed for all protocols.

Results

All LV volumes, function and mass parameters were similar for the three SSFP sequences (P > 0.05 for all). The LV ejection fraction for the 7/3 mm sequence was 67.2 +/- 6.0, 67.4 +/- 5.3 for the 7/0 mm sequence, and the 6/4 mm sequence was 69.2 +/- 5.7. The LV mass ranged from 119.8 +/- 32.4 for the 7/3 mm sequence to 122.2 +/- 34.0 for the 7/0 mm sequence. Variabilities were low with no difference in variability between the sequences.

Conclusion

The three SSFP pulse sequence techniques resulted in similar LV volume, function, and mass measurements with no difference in observer and interstudy variabilities. This may allow application and transfer of LV volume studies and databases based on different imaging parameters, at different CMR sites, with a given post-processing method. Future multi-centre studies may now be in a position to consider multi-vendor study designs for LV volume studies.
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Development of distinct control networks through segregation and integration.

Issue 33 Vol 104 Published on 2007-08-01 PMID 17679691 PMCID PMC1940033
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DOI: https://doi.org/10.1073/pnas.0705843104
Authors: Damien A Fair In X Nico U F Dosenbach In X Jessica A Church In X Alexander L Cohen In X Shefali Brahmbhatt In X Francis M Miezin In X Deanna M Barch In X Marcus E Raichle In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter "integration" of some regions into networks over time while "segregating" other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourette's syndrome.
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Assessment of left atrial volumes at 1.5 Tesla and 3 Tesla using FLASH and SSFP cine imaging.

Issue 4 Vol 9 Published on 2007-07-01 PMID 17578723 PMCID N/A
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DOI: https://doi.org/10.1080/10976640601138805
Authors: L E Hudsmith In X A S H Cheng In X D J Tyler In X C Shirodaria In X J Lee In X S E Petersen In X J M Francis In X Kieran Clarke In X M D Robson In X S Neubauer In X
Abstract:

Purpose

To investigate left atrial volumes and function and their variability in healthy volunteers using steady state free precession (SSFP) and fast low angle shot (FLASH) sequences at both 1.5 and 3 T using both the short-axis and biplane area-length methods.

Materials and methods

Ten healthy volunteers underwent CMR at both 1.5 and 3 Tesla. The biplane area-length method utilized volumes from the horizontal and vertical long axis images.

Results

There were no significant differences between left atrial short-axis volumes or function between 1.5 and 3 T assessed using either FLASH or SSFP sequences. The biplane area-length method underestimated maximal left atrial volume using FLASH by 12 mL at 3 T (18%) and by 10 mL (14%) at 1.5 T (p = 0.003 and p = 0.05 respectively). Variability was larger for left atrial measurements using the biplane area-length method.

Conclusion

Field strength had no effect on left atrial volume and function assessment using either FLASH or SSFP. The use of the short-axis method for the acquisition of left atrial parameters is more reproducible than the biplane area-length for serial measurements.
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[Unused organ donor potential in Denmark].

Issue 26 Vol 169 Published on 2007-06-01 PMID 17725892 PMCID N/A
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DOI: #
Authors: Troels Munch Jørgensen In X Steffen Ellebaek Petersen In X
Abstract: No Abstract Available
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Distinct brain networks for adaptive and stable task control in humans.

Issue 26 Vol 104 Published on 2007-06-01 PMID 17576922 PMCID PMC1904171
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DOI: https://doi.org/10.1073/pnas.0704320104
Authors: Nico U F Dosenbach In X Damien A Fair In X Francis M Miezin In X Alexander L Cohen In X Kristin K Wenger In X Ronny A T Dosenbach In X Michael D Fox In X Abraham Z Snyder In X Justin L Vincent In X Marcus E Raichle In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms.
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Evidence for microvascular dysfunction in hypertrophic cardiomyopathy: new insights from multiparametric magnetic resonance imaging.

Issue 18 Vol 115 Published on 2007-05-01 PMID 17452610 PMCID N/A
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DOI: https://doi.org/10.1161/circulationaha.106.657023
Authors: Steffen E Petersen In X Michael Jerosch-Herold In X Lucy E Hudsmith In X Matthew D Robson In X Jane M Francis In X Helen A Doll In X Joseph B Selvanayagam In X Stefan Neubauer In X Hugh Watkins In X
Abstract:

Background

Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution.

Methods and results

Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001).

Conclusions

In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.
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Dynamic contrast-enhanced MRI before and after transcatheter occlusion of patent foramen ovale.

Issue 3 Vol 188 Published on 2007-03-01 PMID 17312077 PMCID N/A
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DOI: https://doi.org/10.2214/ajr.06.0489
Authors: Oliver K Mohrs In X Steffen E Petersen In X Damir Erkapic In X Anja Victor In X Thomas Schlosser In X Bernd Nowak In X Guenter Kauffmann In X Thomas Voigtlaender In X Hans-Ulrich Kauczor In X
Abstract:

Objective

The purpose of this study was threefold: to evaluate the diagnostic accuracy of dynamic contrast-enhanced MRI compared with transesophageal echocardiography (TEE) in the detection of patent foramen ovale (PFO) and of residual shunts after occlusion of PFO, to define cutoff values for semiquantitative analysis of signal intensity-time curves, and to compare the diagnostic accuracy of visual detection with that of semiquantitative analysis.

Subjects and methods

Forty-three patients (18 women, 25 men; mean age, 51 +/- 14 years) who underwent TEE for suspicion of PFO (n = 26, 19 patients with and seven without PFO) or for routine assessment for residual shunt after transcatheter PFO occlusion (n = 17, nine patients with and eight without residual shunt) were consecutively enrolled to undergo contrast-enhanced MRI (saturation recovery steady-state free precession sequence). The images were analyzed both visually and semiquantitatively for arrival of contrast agent in the left atrium before arrival in the pulmonary veins during a Valsalva maneuver. TEE results were used as the clinical reference.

Results

With an area under the signal intensity-time curve of 0.85, height of the first initial peak in signal intensity in the left atrium proved to be the best discriminator in right-to-left shunt detection. For a cutoff value of 129% (from baseline signal intensity) for this parameter, sensitivity and specificity were 90% (17/19) and 100% (7/7) in patients without PFO devices and 56% (5/9) and 88% (7/8) in patients with PFO devices. The diagnostic accuracy of both visual assessment and semiquantitative analysis was consistently superior before PFO device implantation than after device implantation. The diagnostic accuracy of visual shunt assessment was better than that of semiquantitative shunt assessment in patients with PFO occluders (sensitivity, 67% [6/9] correctly diagnosed; specificity, 88% [7/8]) and those without PFO occluders (sensitivity, 95% [18/19]; specificity, 100% [7/7]).

Conclusion

At present, MRI cannot replace TEE for the exclusion of potential embolic sources, such as thrombus in the left atrial appendage. However, MRI can be an attractive alternative noninvasive technique if TEE is technically unfeasible or is declined by patients.
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A method for using blocked and event-related fMRI data to study "resting state" functional connectivity.

Issue 1 Vol 35 Published on 2007-03-01 PMID 17239622 PMCID PMC2563954
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DOI: https://doi.org/10.1016/j.neuroimage.2006.11.051
Authors: Damien A Fair In X Bradley L Schlaggar In X Alexander L Cohen In X Francis M Miezin In X Nico U F Dosenbach In X Kristin K Wenger In X Michael D Fox In X Abraham Z Snyder In X Marcus E Raichle In X Steven E Petersen In X
Abstract: Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large data sets of task-related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two classes of data sets could potentially be modified to emulate resting state data. These data sets include: (1) "interleaved" resting blocks from blocked or mixed blocked/event-related sets, and (2) residual timecourses from event-related sets that lack rest blocks. Using correlation analysis, we compared the functional connectivity of resting epochs taken from a mixed blocked/event-related design fMRI data set and the residuals derived from event-related data with standard continuous resting state data to determine which class of data can best emulate resting state data. We show that, despite some differences, the functional connectivity for the interleaved resting periods taken from blocked designs is both qualitatively and quantitatively very similar to that of "continuous" resting state data. In contrast, despite being qualitatively similar to "continuous" resting state data, residuals derived from event-related design data had several distinct quantitative differences. These results suggest that the interleaved resting state data such as those taken from blocked or mixed blocked/event-related fMRI designs are well-suited for resting state functional connectivity analyses. Although using event-related data residuals for resting state functional connectivity may still be useful, results should be interpreted with care.
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fMRI reveals novel functional neuroanatomy in a child with perinatal stroke.

Issue 12 Vol 67 Published on 2006-12-01 PMID 17190956 PMCID N/A
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DOI: https://doi.org/10.1212/01.wnl.0000249348.84045.0e
Authors: Damien A Fair In X Timothy T Brown In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Children who have experienced a perinatal stroke often develop normal language function, but the neurobiologic mechanisms underlying this plasticity remain unclear. In this study, we used fMRI to compare, at two ages, the functional neuroanatomy of a child with perinatal stroke with that of age-appropriate cohorts of typically developing children. Although the data for this child are similar to the control group, there are age-dependent differences.
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Time-resolved contrast-enhanced MR angiography of the thorax in adults with congenital heart disease.

Issue 4 Vol 187 Published on 2006-10-01 PMID 16985163 PMCID N/A
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DOI: https://doi.org/10.2214/ajr.05.0403
Authors: Oliver K Mohrs In X Steffen E Petersen In X Thomas Voigtlaender In X Jutta Peters In X Bernd Nowak In X Markus K Heinemann In X Hans-Ulrich Kauczor In X
Abstract:

Objective

The aim of this study was to evaluate the diagnostic value of time-resolved contrast-enhanced MR angiography in adults with congenital heart disease.

Subjects and methods

Twenty patients with congenital heart disease (mean age, 38 +/- 14 years; range, 16-73 years) underwent contrast-enhanced turbo fast low-angle shot MR angiography. Thirty consecutive coronal 3D slabs with a frame rate of 1-second duration were acquired. The mask defined as the first data set was subtracted from subsequent images. Image quality was evaluated using a 5-point scale (from 1, not assessable, to 5, excellent image quality). Twelve diagnostic parameters yielded 1 point each in case of correct diagnosis (binary analysis into normal or abnormal) and were summarized into three categories: anatomy of the main thoracic vessels (maximum, 5 points), sequential cardiac anatomy (maximum, 5 points), and shunt detection (maximum, 2 points). The results were compared with a combined clinical reference comprising medical or surgical reports and other imaging studies. Diagnostic accuracies were calculated for each of the parameters as well as for the three categories.

Results

The mean image quality was 3.7 +/- 1.0. Using a binary approach, 220 (92%) of the 240 single diagnostic parameters could be analyzed. The percentage of maximum diagnostic points, the sensitivity, the specificity, and the positive and the negative predictive values were all 100% for the anatomy of the main thoracic vessels; 97%, 87%, 100%, 100%, and 96% for sequential cardiac anatomy; and 93%, 93%, 92%, 88%, and 96% for shunt detection.

Conclusion

Time-resolved contrast-enhanced MR angiography provides, in one breath-hold, anatomic and qualitative functional information in adult patients with congenital heart disease. The high diagnostic accuracy allows the investigator to tailor subsequent specific MR sequences within the same session.
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Functional and structural vascular remodeling in elite rowers assessed by cardiovascular magnetic resonance.

Issue 4 Vol 48 Published on 2006-08-01 PMID 16904551 PMCID N/A
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DOI: https://doi.org/10.1016/j.jacc.2006.04.078
Authors: Steffen E Petersen In X Frank Wiesmann In X Lucy E Hudsmith In X Matthew D Robson In X Jane M Francis In X Joseph B Selvanayagam In X Stefan Neubauer In X Keith M Channon In X
Abstract:

Objectives

We aimed to noninvasively quantify the effects of chronic exercise training on both peripheral and central conduit artery function and structure with high-resolution magnetic resonance imaging (MRI).

Background

Physical activity has well-known beneficial effects on vascular function in subjects with endothelial dysfunction. Exercise also leads to beneficial effects on endothelial function in elderly athletes, possibly contributing toward the reduced risk from coronary artery disease in this age group. However, conflicting data exist on the training effects in the younger population.

Methods

A total of 49 young (age 20 to 35 years) nonsmoking subjects, comprising elite rowers and age- and gender-matched sedentary control subjects, underwent MRI (1.5-T). The ascending, the proximal descending, and the distal descending aorta, and the common carotid artery and the brachial artery were assessed for diastolic and systolic area and distensibility. Endothelial-dependent and -independent brachial artery dilatation were also assessed by cine MRI.

Results

Rowers showed vascular remodeling with enlarged brachial (by 51%, p < 0.001) and reduced central conduit artery cross-sectional areas (by up to 28% [e.g., distal descending aorta], p < 0.001). Vessel distensibilities (mm Hg(-1)) were similar for elite rowers when compared with sedentary control subjects at all levels of the aorta and the carotid and brachial artery (p > 0.05 for all). Endothelial-dependent dilation (percentage and mm2) was similar for rowers and control subjects (p > 0.05). However, rowers showed reduced absolute (by 33%) endothelial-independent dilation (p < 0.001).

Conclusions

Young elite rowers demonstrate normal endothelial-dependent but reduced endothelial-independent dilation. Chronic, whole body, combined endurance- and strength-training does not lead to changes in arterial stiffness but to vascular remodeling.
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Sex-specific characteristics of cardiac function, geometry, and mass in young adult elite athletes.

Issue 2 Vol 24 Published on 2006-08-01 PMID 16823779 PMCID N/A
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DOI: https://doi.org/10.1002/jmri.20633
Authors: Steffen E Petersen In X Lucy E Hudsmith In X Matthew D Robson In X Helen A Doll In X Jane M Francis In X Frank Wiesmann In X Bernd A Jung In X Juergen Hennig In X Hugh Watkins In X Stefan Neubauer In X
Abstract:

Purpose

To study young adult elite athletes with age- and sex-matched sedentary controls to assess sex-specific differences for left ventricular (LV) and right ventricular (RV) volumes and mass as well as for LV contraction and relaxation.

Materials and methods

A total of 23 male athletes (mean age 25 +/- 4 years, training 22 +/- 7 hours/week in rowing, swimming, or triathlon) and 20 female athletes (mean age 24 +/- 4 years, training 19 +/- 5 hours/week in rowing, swimming, or triathlon) and age- and sex-matched sedentary controls (21 male/17 female) underwent cardiovascular magnetic resonance (CMR) imaging (1.5 Tesla). Cardiac phase contrast imaging using a black-blood k-space segmented gradient echo sequence was used for analysis of cardiac contraction and relaxation and steady-state free-precession cine images were acquired for determination of cardiac volumes and mass.

Results

Male and female athletes showed similar increases in LV and RV volume and mass indices when compared to controls (ranging between 15% and 42%). No sex-specific differences in training effect on LV and RV volumes, mass indices, and ejection fractions, as well as LV to RV ratios of these volume and mass indices (parameters of balanced LV and RV dilatation and hypertrophy) were observed (all P for interaction >0.05). Similarly, no sex-specific differences in training effect on cardiac contraction and relaxation were found (all P for interaction >0.05).

Conclusion

Young adult elite athletes do not show sex-specific adaptive structural and functional changes to exercise training in accordance with the benign nature of the hypertrophy associated with athlete's heart.
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Determination of cardiac volumes and mass with FLASH and SSFP cine sequences at 1.5 vs. 3 Tesla: a validation study.

Issue 2 Vol 24 Published on 2006-08-01 PMID 16795076 PMCID N/A
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DOI: https://doi.org/10.1002/jmri.20638
Authors: Lucy E Hudsmith In X Steffen E Petersen In X Damian J Tyler In X Jane M Francis In X Adrian S H Cheng In X Kieran Clarke In X Joseph B Selvanayagam In X Matthew D Robson In X Stefan Neubauer In X
Abstract:

Purpose

To compare cardiac cine MR imaging using steady state free precession (SSFP) and fast low angle shot (FLASH) techniques at 1.5 and 3 T, and to establish their variabilities and reproducibilities for cardiac volume and mass determination in volunteers. To assess the feasibility of SSFP imaging in patients at 3 T and to determine comparability to volume data acquired at 1.5 T.

Materials and methods

Ten healthy volunteers underwent cardiac magnetic resonance imaging using SSFP and segmented gradient-echo FLASH, using both a 1.5 and a 3 T MR system on the same day. Ten patients with impaired left ventricular (LV) function were also studied at both field strengths with SSFP.

Results

For both SSFP and FLASH, field strength had no effect on the quantification of LV and right ventricular (RV) volumes, mass, or function (P > or = 0.05 for field strength for all parameters). At both 1.5 and 3 T, SSFP yielded smaller LV mass (e.g., at 3 T 109 +/- 30 g vs. 142 +/- 37 g; P = 0.011) and larger LV volume (e.g., at 3 T end-diastolic volume 149 +/- 37 mL vs. 133 +/- 31 mL at 5 T; P = 0.041) measurements than FLASH. In patients with reduced LV function, all volume and mass measurements were again similar for SSFP sequences at 1.5 vs. 3 T. In volunteers and patients, measurement variabilities for LV parameters were small for both field strength and sequences, ranging between 3.7% and 10.7% for mass.

Conclusion

Compared to 1.5 T, cardiac cine MR imaging at 3 T, using either FLASH or SSFP sequences, is feasible and highly reproducible. Field strength does not have an influence on quantification of cardiac volume or mass, but the systematic overestimation of LV mass and underestimation of LV volume by FLASH compared to SSFP is present at both 1.5 and 3 T. Normal values for cardiac volumes and mass established at 1.5 T can be applied to scans obtained at 3 T.
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Evidence for separate perceptual reactivation and search processes during remembering.

Issue 7 Vol 16 Published on 2006-07-01 PMID 16162854 PMCID N/A
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DOI: https://doi.org/10.1093/cercor/bhj037
Authors: Mark E Wheeler In X Gordon L Shulman In X Randy L Buckner In X Francis M Miezin In X Katerina Velanova In X Steven E Petersen In X
Abstract: Remembering involves the coordinated recruitment of strategic search processes and processes involved in reconstructing the content of the past experience. In the present study we used a cueing paradigm based on event-related functional magnetic resonance imaging to separate activity in the initial preparation phases of retrieval from later phases during which retrieval search ensued, and detailed auditory and visual memories were reconstructed. Results suggest a dissociation among inferior temporal (IT) and parieto-occipital (PO) processing regions in how they were influenced by preparatory cues prior to remembering, and indicate a dissociation in how they were influenced by the subsequent validity of those cues during remembering. Regions in IT cortex appeared to show search-related activity during retrieval, as well as robust modality effects, but they were not influenced by preparatory cues. These findings suggest a specific role for IT regions in reconstruction of visual details during remembering. While dorsal regions in parietal and superior occipital cortex also appeared to show search-related activity as well as robust modality effects, they were also influenced by preparatory cues during the retrieval phase, and to a lesser degree during the cue phase. These findings indicate a role in integrating perceptual reactivation and search processes during remembering.
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A core system for the implementation of task sets.

Issue 5 Vol 50 Published on 2006-06-01 PMID 16731517 PMCID PMC3621133
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DOI: https://doi.org/10.1016/j.neuron.2006.04.031
Authors: Nico U F Dosenbach In X Kristina M Visscher In X Erica D Palmer In X Francis M Miezin In X Kristin K Wenger In X Hyunseon C Kang In X E Darcy Burgund In X Ansley L Grimes In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: When performing tasks, humans are thought to adopt task sets that configure moment-to-moment data processing. Recently developed mixed blocked/event-related designs allow task set-related signals to be extracted in fMRI experiments, including activity related to cues that signal the beginning of a task block, "set-maintenance" activity sustained for the duration of a task block, and event-related signals for different trial types. Data were conjointly analyzed from mixed design experiments using ten different tasks and 183 subjects. Dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) showed reliable start-cue and sustained activations across all or nearly all tasks. These regions also carried the most reliable error-related signals in a subset of tasks, suggesting that the regions form a "core" task-set system. Prefrontal regions commonly related to task control carried task-set signals in a smaller subset of tasks and lacked convergence across signal types.
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Hypertrophic cardiomyopathy in Noonan Syndrome closely mimics familial hypertrophic cardiomyopathy due to sarcomeric mutations.

Issue 3-4 Vol 22 Published on 2006-06-01 PMID 16267621 PMCID N/A
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DOI: https://doi.org/10.1007/s10554-005-9034-y
Authors: Lucy E Hudsmith In X Steffen E Petersen In X Jane M Francis In X Matthew D Robson In X Hugh Watkins In X Stefan Neubauer In X
Abstract: A 27 year old female with Noonan syndrome and hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. These images showed asymmetrical septal hypertrophy with maximal left ventricular end-diastolic wall thickness of 25 mm. Following administration of gadolinium, areas of hyperenhancement were seen in the anterior, anteroseptal and lateral walls. This is the first report of focal gadolinium hyperenhancement in hypertrophic cardiomyopathy due to Noonan syndrome and suggests that myocardial fibrosis can be imaged by MR hyperenhancement as seen previously in sarcomeric hypertrophic cardiomyopathy.
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Development of letter-specific processing: the effect of reading ability.

Issue 1 Vol 122 Published on 2006-05-01 PMID 16414004 PMCID N/A
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DOI: https://doi.org/10.1016/j.actpsy.2005.11.005
Authors: E Darcy Burgund In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: During development, perceptual processing is tuned to inputs in the environment such that certain frequently encountered classes of stimuli are processed more effectively than similar comparison stimuli. Letters represent a class of stimuli that are encountered frequently in the environment, at least in literate cultures. Thus, the present study examined the development of letter-specific processing in children 6-19 years old by comparing the difference between performance on a letter-matching task and an unfamiliar non-letter-matching task in different subject groups. Results revealed an increase in letter-specific processing with development. Moreover, comparisons of letter-specific processing in groups of subjects matched either in age or reading ability indicate that the emergence of letter-specific processing is linked to increased reading skill, rather than increased age per se. Findings support theories of perceptual expertise, which suggest that skilled processing drives the specialization of perceptual mechanisms for certain classes of stimuli.
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Myocardial tissue phase mapping with cine phase-contrast mr imaging: regional wall motion analysis in healthy volunteers.

Issue 3 Vol 238 Published on 2006-03-01 PMID 16424246 PMCID N/A
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DOI: https://doi.org/10.1148/radiol.2383041992
Authors: Steffen E Petersen In X Bernd A Jung In X Frank Wiesmann In X Joseph B Selvanayagam In X Jane M Francis In X Juergen Hennig In X Stefan Neubauer In X Matthew D Robson In X
Abstract:

Purpose

To establish prospectively a database of normal three-dimensional systolic and diastolic endocardial and epicardial velocity values for all myocardial segments in healthy volunteers by using cine phase-contrast velocity magnetic resonance imaging, also called tissue phase mapping (TPM).

Materials and methods

The study was approved by the institutional ethics committee and was conducted according to principles of the Declaration of Helsinki; each subject provided informed written consent. Ninety-six healthy volunteers (57 [59%] men, 39 [41%] women; mean age, 38 years +/- 12 [standard deviation]) underwent cardiac phase-contrast imaging with a black blood segmented k-space gradient-echo sequence for the analysis of three-dimensional myocardial velocity with high spatial resolution at 1.5 T on basal, midventricular, and apical short-axis views. Eighteen consecutive volunteers were imaged twice to determine interstudy reproducibility, and intra- and interobserver variability values were analyzed. Systolic and diastolic velocity curves were analyzed for peak velocity and time to peak velocity in the radial, circumferential, and longitudinal directions, as well as for torsion rate and longitudinal strain rate. Mixed-effects models with a random intercept for volunteers were used to test differences among the three ventricular sections and the transmural, endocardial, and epicardial parameters.

Results

TPM enabled reproducible assessment of myocardial velocity with small intra- and interobserver variability values. Systolic peak radial velocity was lowest at the apical level (P < .001); diastolic peak radial velocity was similar at all three myocardial levels (P = .73). As viewed from the apex, a relative counterclockwise rotation during systole was followed by a relative clockwise rotation of the apex against the base. Diastolic and systolic peak longitudinal velocity values decreased from base to apex (P < .001). A gradient between endocardium and epicardium was observed for radial velocity values, with greater endocardial velocity values (P < .001).

Conclusion

TPM is a reproducible comprehensive modality for assessment of regional wall motion, and intra- and interobserver variability values are low.
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Percutaneous left atrial appendage transcatheter occlusion (PLAATO): planning and follow-up using contrast-enhanced MRI.

Issue 2 Vol 186 Published on 2006-02-01 PMID 16423938 PMCID N/A
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DOI: https://doi.org/10.2214/ajr.04.1875
Authors: Oliver K Mohrs In X Rainer Schraeder In X Steffen E Petersen In X Detlef Scherer In X Bernd Nowak In X Hans-Ulrich Kauczor In X Thomas Voigtlaender In X
Abstract: No Abstract Available
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The development of sustained and transient neural activity.

Issue 3 Vol 29 Published on 2006-02-01 PMID 16236529 PMCID N/A
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DOI: https://doi.org/10.1016/j.neuroimage.2005.08.056
Authors: E Darcy Burgund In X Heather M Lugar In X Francis M Miezin In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: Sustained and transient signals were compared in a group of 7-8-year-old children and a group of adults performing the same cognitive task using functional magnetic resonance imaging (fMRI) in conjunction with a mixed blocked/event-related design. Results revealed several regions, including a region in the right lateral inferior frontal gyrus, that exhibited opposing developmental trajectories in sustained and transient signals--in particular, decreased sustained signals and increased transient signals with age. Re-analysis of the data assuming "blocked" and "event-related" designs, as opposed to a mixed design, produced different results. In combination, these results may help to explain contradictory findings in the literature regarding the direction of neural development in frontal cortex. Moreover, these results underscore the value of separating sustained and transient signals in fMRI studies of development.
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A comparison of analysis of variance and correlation methods for investigating cognitive development with functional magnetic resonance imaging.

Issue 1 Vol 30 Published on 2006-01-01 PMID 16925474 PMCID N/A
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DOI: https://doi.org/10.1207/s15326942dn3001_2
Authors: Damien A Fair In X Timothy T Brown In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: Statistical approaches used in functional magnetic resonance imaging (fMRI) to study cognitive development are varied and evolving. Two approaches have generally been used. These are between-group end-point analysis of variance (ANOVA) and age-related regression. Differences in these 2 approaches could produce different results when applied to a single data set. Event-related fMRI data from a group of typically developing participants (n = 95; age range = 7-35 years) performing controlled lexical processing tasks were analyzed using both methods. Results from the 2 approaches showed significant overlap, but also noteworthy differences. The results suggest that for regions showing age-related changes, correlation was relatively more sensitive to more linear changes whereas ANOVA was relatively more sensitive to less-linear changes. These findings suggest that full characterization of developmental dynamics will require converging methodologies.
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Cardiac cine MR-imaging at 3T: FLASH vs SSFP.

Issue 5 Vol 8 Published on 2006-01-01 PMID 16891230 PMCID N/A
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DOI: https://doi.org/10.1080/10976640600723797
Authors: Damian J Tyler In X Lucy E Hudsmith In X Steffen E Petersen In X Jane M Francis In X Peter Weale In X Stefan Neubauer In X Kieran Clarke In X Matthew D Robson In X
Abstract: The implications of an increase in field strength, from 1.5 T to 3 T, for routine functional cardiac examinations have been systematically investigated. Flip angle optimization was carried out for identical SSFP and FLASH cine imaging sequences at 1.5 T and 3 T, which supported the use of 20 degrees (FLASH 1.5 T and 3 T) and >60 degrees (SSFP 1.5 T and 3 T). The optimized sequences were applied in a study of cardiac function in a group of ten normal volunteers. Both SSFP and FLASH sequences showed significant SNR increases in the myocardium and blood at 3 T compared with 1.5 T, increases of 48% and 30% (myocardium and blood, respectively) for the SSFP sequence and 19% and 13% for the FLASH sequence. The SSFP sequence also showed a significant increase in CNR (22%). Image quality assessment revealed that the SSFP acquisitions were superior to FLASH at both field strengths. Although SSFP contained more artifacts at 3 T, they would not prevent its clinical use. We conclude that cardiac functional examinations at 3 T should use SSFP sequences.
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Does human functional brain organization shift from diffuse to focal with development?

Issue 1 Vol 9 Published on 2006-01-01 PMID 16445388 PMCID N/A
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DOI: https://doi.org/10.1111/j.1467-7687.2005.00455.x
Authors: Timothy T Brown In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: No Abstract Available
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Thrombus detection in the left atrial appendage using contrast-enhanced MRI: a pilot study.

Issue 1 Vol 186 Published on 2006-01-01 PMID 16357402 PMCID N/A
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DOI: https://doi.org/10.2214/ajr.04.1504
Authors: Oliver K Mohrs In X Bernd Nowak In X Steffen E Petersen In X Matthias Welsner In X Christine Rubel In X Annett Magedanz In X Hans-Ulrich Kauczor In X Thomas Voigtlaender In X
Abstract:

Objective

Left atrial thrombi are an important cause for embolism-related morbidity and mortality. Transesophageal echocardiography (TEE), the clinical reference, is semiinvasive; thus, we aimed to assess the value of contrast-enhanced cardiovascular MRI for the detection of thrombus in the left atrial appendage.

Conclusion

The image quality was good for both 2D perfusion (grade 4 +/- 1) and 3D turbo fast low-angle shot (FLASH) (grade 4 +/- 1, n.s.). Compared with TEE, 2D perfusion, 3D turboFLASH, and the combination of both techniques yielded sensitivities of 47/35/44%, specificities of 50/67/67%, positive predictive values of 73/75/80%, and negative predictive values of 25/27/29%, respectively. The size of the thrombus was overestimated by 2D perfusion (66%) and by 3D turboFLASH (25%) and agreement for location and shape of thrombus was 50% and 75% for 2D perfusion and 75% and 50% for 3D turboFLASH, respectively. The TEE thrombus size was significantly larger in patients with true-positive diagnoses by 2D perfusion (148%) and by 3D turboFLASH (151%) when compared with patients with false-negative diagnoses (p < 0.05 for both). No such difference was found for image quality, time delay between TEE and MRI examination, and location and shape of thrombi. Contrast-enhanced MRI lacks diagnostic accuracy for the detection of thrombi in the left atrial appendage. Future technical improvements are essential to establish this technique as a noninvasive alternative to TEE.
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Intermanual transfer effects in sequential tactuomotor learning: evidence for effector independent coding.

Issue 6 Vol 44 Published on 2006-01-01 PMID 16198379 PMCID N/A
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DOI: https://doi.org/10.1016/j.neuropsychologia.2005.08.010
Authors: Hanneke I van Mier In X Steven E Petersen In X
Abstract: Results from our earlier brain imaging studies regarding motor learning have shown different areas activated during naive and practiced performance. When right handed participants moved a pen either with the dominant or non-dominant hand continuously through a cut-out maze as quickly and accurately as possible, practice resulted in decreased brain activity in right premotor and parietal areas as well as left cerebellum, while increased activity was found in the supplementary motor area (SMA). These lateralized practiced-related changes in brain activation suggest effector-independent abstract coding of information. To test this hypothesis more extensively, intermanual transfer of learning was examined in 24 male and female participants (12 right- and 12 left-handed) using the same maze-learning task. It was hypothesized that if an abstract representation of the movement is learned and stored, intermanual transfer effects should be more pronounced when participants transferred to a same maze as opposed to a mirror image of the maze. Errors and velocity were measured during the following conditions: initial naive performance (Naive); after practice on the maze (Prac); during intermanual transfer to the same maze (Transfer Identical); and to the mirror maze (Transfer Mirror). Transfer direction was tested from the dominant to non-dominant hand and vice versa. No significant differences were found between right- and left-handed participants, males and females, and transfer directions. However, intermanual transfer of learning was significantly greater to the identical maze as opposed to the mirror maze. These results showed that learning was indeed taking place at an abstract effector independent level.
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Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment.

Issue 21 Vol 112 Published on 2005-11-01 PMID 16286587 PMCID N/A
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DOI: https://doi.org/10.1161/circulationaha.105.549170
Authors: Joseph B Selvanayagam In X Michael Jerosch-Herold In X Italo Porto In X David Sheridan In X Adrian S H Cheng In X Steffen E Petersen In X Nick Searle In X Keith M Channon In X Adrian P Banning In X Stefan Neubauer In X
Abstract:

Background

Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium.

Methods and results

Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001). Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI (z=2.0, P=0.04).

Conclusions

CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.
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Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging.

Issue 1 Vol 46 Published on 2005-07-01 PMID 15992642 PMCID N/A
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DOI: https://doi.org/10.1016/j.jacc.2005.03.045
Authors: Steffen E Petersen In X Joseph B Selvanayagam In X Frank Wiesmann In X Matthew D Robson In X Jane M Francis In X Robert H Anderson In X Hugh Watkins In X Stefan Neubauer In X
Abstract:

Objectives

We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction (LVNC) from lesser degrees of trabecular layering seen in healthy volunteers and, in those with cardiomyopathies and concentric left ventricular hypertrophy, potential differential diagnoses. We hypothesized that pathological trabeculation could be distinguished by determining the ratio of non-compacted to compacted myocardium (NC/C ratio).

Background

Left ventricular non-compaction is characterized by a non-compacted myocardial layer in the left ventricle. Cardiovascular magnetic resonance images this layer with unprecedented quality, particularly in the ventricular apex, where echocardiography has inherent difficulties.

Methods

We analyzed magnetic resonance cine images, using the 17-segment model in 45 healthy volunteers, 25 athletes, 39 patients with hypertrophic cardiomyopathy and 14 with dilated cardiomyopathy, 17 with hypertensive heart disease, and 30 with aortic stenosis, as well as images from 7 patients previously diagnosed with LVNC whose diagnoses were supported by additional features.

Results

Areas of non-compaction were common and occurred more frequently in all groups studied in apical and lateral, rather than in basal or septal, segments. A NC/C ratio of >2.3 in diastole distinguished pathological non-compaction, with values for sensitivity, specificity, and positive and negative predictions of 86%, 99%, 75%, and 99%, respectively.

Conclusions

Left ventricular non-compaction is diagnosed accurately with CMR using the NC/C ratio in diastole.
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Quantification of resting myocardial blood flow in a pig model of acute ischemia based on first-pass MRI.

Issue 5 Vol 53 Published on 2005-05-01 PMID 15844154 PMCID N/A
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DOI: https://doi.org/10.1002/mrm.20457
Authors: Melanie Schmitt In X Georg Horstick In X Steffen E Petersen In X Andrea Karg In X Nico Hoffmann In X Thorsten Gumbrich In X Nico Abegunewardene In X Wolfgang G Schreiber In X
Abstract: Qualitative and semiquantitative contrast-enhanced (CE) dynamic perfusion MRI techniques are established as noninvasive diagnostic means of assessing coronary artery disease. However, to date quantification of myocardial blood flow (MBF) has not reached the same acceptance as MBF quantification with nuclear techniques. To validate quantification of MBF at rest using the extracellular contrast agent (CA) Gd-DTPA, we performed an animal study in a pig model of acute myocardial ischemia. We quantified MBF from MRI data with a mathematical model (MMID4) of the underlying vasculature. These MBF results were subsequently compared with the results from fluorescent microspheres. The study showed a correlation of r = 0.66 between MBF estimates obtained with MRI and those obtained with fluorescent microspheres. The correlation for ischemic and nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion, quantification of resting MBF using MMID4 is a valid method under conditions of acute myocardial ischemia.
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Eating disorders and emotional and physical well-being: associations between student self-reports of eating disorders and quality of life as measured by the SF-36.

Issue 3 Vol 14 Published on 2005-04-01 PMID 16022064 PMCID N/A
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DOI: https://doi.org/10.1007/s11136-004-0792-0
Authors: Helen A Doll In X Sophie E Petersen In X Sarah L Stewart-Brown In X
Abstract:

Objective

To assess health-related quality of life (HRQoL) in subjects with eating disorders in terms of eating disorder type and in relation to self-reports of longstanding illness, depression and self-harming behaviours.

Method

Data on eating disorder history, SF-36 health status, longstanding illness, and self-reported frequencies of depression, self-harming behaviour, and suicidal thoughts or acts were collected during 1996 as part of a UK postal survey of students' health. Completed questionnaires were returned by 1439 of 3750 students (response rate 42%).

Results

Eighty-three respondents (5.8%; 8.9% of females) reported a probable eating disorder history: 54 (3.8%) bulimia nervosa, 22 (1.6%) binge eating disorder, and 7 (0.5%) anorexia nervosa. Eating disorder subjects reported more impairment in SF-36 emotional than physical well-being, with significantly lower mental (p < 0.001) but not physical (p = 0.21) component summary scores. This was most evident in bulimia nervosa and binge eating disorder subjects. Anorexia nervosa subjects reported fewer SF-36 emotional limitations although they were significantly more likely to report depression, self-harming behaviour, and suicidal ideation.

Discussion

An eating disorder history is accompanied by HRQoL impairment primarily in emotional well-being. Anorexia nervosa subjects perceive fewer limitations than subjects with other eating disorders. While this is consistent with previous reports of better SF-36 emotional well-being in those with restrictive eating behaviours, it may also suggest that the SF-36 is insensitive to emotional distress in anorexia nervosa.
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Task demands modulate sustained and transient neural activity during visual-matching tasks.

Issue 2 Vol 25 Published on 2005-04-01 PMID 15784430 PMCID N/A
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DOI: https://doi.org/10.1016/j.neuroimage.2004.12.039
Authors: E Darcy Burgund In X Heather M Lugar In X Bradley L Schlaggar In X Steven E Petersen In X
Abstract: The extent to which a task demands verbal or non-verbal processing may influence which neural regions underlie performance. In the present study, sustained and transient responses were examined using functional magnetic resonance imaging (fMRI) in conjunction with a mixed blocked/event-related design during three visual-matching tasks that varied in the extent to which they relied on verbal processing. In a name-matching task, subjects decided whether two letters had the same or a different name (e.g., A a); in a physical-matching task, subjects decided whether two letters were exactly the same or different (e.g., A A); in a non-letter-matching task, subjects decided whether two non-letters were exactly the same or different. Results revealed several regions in which sustained activity differed across the three tasks as well as several regions in which sustained activity did not differ. Most notably, regions in the right inferior frontal gyrus exhibited greater sustained activity during the name-matching task than during the physical or non-letter-matching tasks, indicating that sustained activity in this region is sensitive to the amount of verbal processing required by a particular task. Moreover, transient activity in the right inferior frontal regions, as well as others, exhibited the opposite pattern of results. In combination, results suggest that sustained and transient activities interact to produce the context-appropriate response during visual-matching tasks.
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Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: insights from cardiovascular magnetic resonance imaging.

Issue 8 Vol 111 Published on 2005-03-01 PMID 15723982 PMCID N/A
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DOI: https://doi.org/10.1161/01.cir.0000156328.28485.ad
Authors: Joseph B Selvanayagam In X Italo Porto In X Keith Channon In X Steffen E Petersen In X Jane M Francis In X Stefan Neubauer In X Adrian P Banning In X
Abstract:

Background

Although troponin elevation after percutaneous coronary intervention (PCI) is common, uncertainties remain about the mechanisms of its release and its relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of the heart has been shown to reliably quantify areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac troponin release, we studied the incidence and extent of new irreversible injury in patients undergoing PCI and correlated it to postprocedural changes in cardiac troponin I.

Methods and results

Fifty patients undergoing PCI were studied with preprocedural and postprocedural (24 hours) delayed-enhancement MRI for assessment of new irreversible myocardial injury. Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI. Of these 50 patients, 24 underwent a further third MRI scan at a median of 8 months after the procedure. Mean patient age was 64+/-12 years. After the procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement, with a mean mass of 6.0+/-5.8 g, or 5.0+/-4.8% of total left ventricular mass. All of these patients had raised troponin I levels (range 1.0 to 9.4 mug/L). Thirty-four patients (68%) had no elevated troponin I and no evidence of new myocardial necrosis on MRI. There was a strong correlation between the rise in troponin I measurements at 24 hours and mean mass of new myocardial hyperenhancement, both early (r=0.84; P<0.001) and late (r=0.71; P<0.001) after PCI, although there was a trend for a reduction in the size of PCI-induced myocardial injury in the late follow-up scan (P=0.07).

Conclusions

In the setting of PCI, patients demonstrating postprocedural elevation in troponin I have evidence of new irreversible myocardial injury on delayed-enhancement MRI. The magnitude of this injury correlates directly with the extent of troponin elevation.
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Developmental changes in human cerebral functional organization for word generation.

Issue 3 Vol 15 Published on 2005-03-01 PMID 15297366 PMCID N/A
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DOI: https://doi.org/10.1093/cercor/bhh129
Authors: Timothy T Brown In X Heather M Lugar In X Rebecca S Coalson In X Fran M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: A fundamental issue in cognitive neuroscience is the nature of developmental changes in human cerebral functional organization for higher cognitive functions. Event-related functional magnetic resonance imaging was used to measure developmental changes in the functional neuroanatomy subserving controlled lexical association. First, brain regions showing significant differences in activity between school-age children and young adults, despite equivalent task performance, were identified. Then, activity in these regions was more fully characterized in individuals spanning the ages of 7-32 years old. Cross-sectional and regression analyses showed systematic increases and decreases in levels of activity over age, by region. Age-related increases in activity were primarily newly recruited, later-stage processing regions, such as in left frontal and left parietal cortex. Decreases, on the other hand, were all positive activations that attenuated with age and were found across a wider neuroanatomical range, including earlier processing regions such as bilateral extrastriate cortex. The hemodynamic magnitude, neuroanatomical location and maturational timecourse of these progressive and regressive changes have implications for models of the developing specialization in human cerebral functional organization.
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Relationship of irreversible myocardial injury to troponin I and creatine kinase-MB elevation after coronary artery bypass surgery: insights from cardiovascular magnetic resonance imaging.

Issue 4 Vol 45 Published on 2005-02-01 PMID 15708715 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1016/j.jacc.2004.11.030
Authors: Joseph B Selvanayagam In X David Pigott In X Lognathen Balacumaraswami In X Steffen E Petersen In X Stefan Neubauer In X David P Taggart In X
Abstract: No Abstract Available
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Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging.

Issue 5 Vol 7 Published on 2005-01-01 PMID 16353438 PMCID N/A
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DOI: https://doi.org/10.1080/10976640500295516
Authors: Lucy E Hudsmith In X Steffen E Petersen In X Jane M Francis In X Matthew D Robson In X Stefan Neubauer In X
Abstract:

Purpose

The aim of this project was to establish a database of left and right ventricular and left atrial dimensions in healthy volunteers using steady-state free precession cardiac magnetic resonance imaging, the clinical technique of choice, across a wide age range.

Methods

108 healthy volunteers (63 male, 45 female) underwent cardiac magnetic resonance imaging using steady-state free precession sequences. Manual analysis was performed by 2 experienced observers.

Results

Left and right ventricular volumes and left ventricular mass were larger in males than females: LV end-diastolic volume 160 +/- 29 mL vs. 135 +/- 26 mL, LV end-systolic volume 50 +/- 16 mL vs. 42 +/- 12 mL; RV end-diastolic volume 190 +/- 33 mL vs. 148 +/- 35 mL, RV end-systolic volume 78 +/- 20 mL vs. 56 +/- 18 mL (p < .05 for all). Normalization of values to body surface area removed the statistical differences for LV volumes, but not for LV mass or RV volumes. With increased age, males showed a significant decrease in volume and mass indices for both ventricles, while female values remained unchanged. Compared to females, males had significantly larger maximal left atrial volumes (103 +/- 30 mL vs. 89 +/- 21 mL, p = .01) and left atrial stroke volumes (58 +/- 23 mL vs. 48 +/- 15 mL, p = .01). There was no difference in left atrial ejection fraction between the sexes.

Conclusion

We have produced a large database of age-related normal ranges for left and right ventricular function and left atrial function in males and females. This will allow accurate interpretation of clinical and research datasets.
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Differentiation of athlete's heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance.

Issue 3 Vol 7 Published on 2005-01-01 PMID 15959967 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1081/jcmr-200060631
Authors: Steffen E Petersen In X Joseph B Selvanayagam In X Jane M Francis In X Saul G Myerson In X Frank Wiesmann In X Matthew D Robson In X Ingegerd Ostman-Smith In X Barbara Casadei In X Hugh Watkins In X Stefan Neubauer In X
Abstract:

Purpose

Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging.

Methods

A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined.

Results

Left ventricular (LV) mass indices were similar for all forms of LVH (p > 0.05), which were at least 35% higher than those obtained in healthy volunteers (p < 0.05). Multiple logistic regression showed that the percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive heart disease. Using a receiver operating curve-determined cut-off value for diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes' hearts could be differentiated from all forms of pathological cardiac hypertrophy with 99% specificity.

Conclusions

Athlete's heart can be reliably distinguished from all forms of pathological cardiac hypertrophy using CMR-derived LV volume and geometric indices, but pathological forms of LVH present with overlapping cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical value.
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Diagnosis of patent foramen ovale using contrast-enhanced dynamic MRI: a pilot study.

Issue 1 Vol 184 Published on 2005-01-01 PMID 15615982 PMCID N/A
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Keywords:
DOI: https://doi.org/10.2214/ajr.184.1.01840234
Authors: Oliver K Mohrs In X Steffen E Petersen In X Damir Erkapic In X Christine Rubel In X Rainer Schräder In X Bernd Nowak In X W Andreas Fach In X Hans-Ulrich Kauczor In X Thomas Voigtlaender In X
Abstract:

Objective

The aim of this study was to evaluate the feasibility of dynamic contrast-enhanced MRI for detection of patent foramen ovale.

Subjects and methods

Fifteen patients with and five patients without patent foramen ovale underwent transesophageal echocardiography and MRI, which were performed during the Valsalva maneuver. Grading results (grade 0, no patent foramen ovale and grades 1-3, minor to major enhancement due to intracardiac shunt) were assessed visually. Signal-intensity curves in the left atrium and in a pulmonary vein served to underline the diagnosis.

Results

The diagnoses of all patients with (15/15) and without patent foramen ovale (5/5) were correct compared with the findings of the reference transesophageal echocardiography. In 12 (60%) of 20 patients, the grading scores were identical, and in four (20%) of 20 patients, the scores differed by more than one grade. Overall, there was a good correlation of grading scores (r = 0.7, p < 0.05). Using signal-intensity curves, we found that the patients with patent foramen ovale showed an additional signal peak in the left atrium before the enhancement of the pulmonary vein because of an intracardiac shunt. In three of 15 patients with patent foramen ovale, an atrial septal aneurysm was correctly diagnosed.

Conclusion

This pilot study shows that MRI is a new noninvasive method to detect patent foramen ovale and atrial septal aneurysm. A grading is possible but warrants further investigation regarding its predictive value and impact on treatment strategies.
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Subendocardial and papillary muscle involvement in a patient with Churg-Strauss syndrome, detected by contrast enhanced cardiovascular magnetic resonance.

Issue 1 Vol 91 Published on 2005-01-01 PMID 15604316 PMCID PMC1768616
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DOI: https://doi.org/10.1136/hrt.2004.050070
Authors: S E Petersen In X A Kardos In X S Neubauer In X
Abstract: No Abstract Available
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Left ventricular thrombi in a patient with left ventricular non-compaction in visualisation of the rationale for anticoagulation.

Issue 1 Vol 91 Published on 2005-01-01 PMID 15604311 PMCID PMC1768651
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DOI: https://doi.org/10.1136/hrt.2004.045971
Authors: S E Petersen In X J Timperley In X S Neubauer In X
Abstract: No Abstract Available
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Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution magnetic resonance imaging.

Issue 10 Vol 44 Published on 2004-11-01 PMID 15542292 PMCID N/A
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DOI: https://doi.org/10.1016/j.jacc.2004.08.033
Authors: Frank Wiesmann In X Steffen E Petersen In X Paul M Leeson In X Jane M Francis In X Matthew D Robson In X Qian Wang In X Robin Choudhury In X Keith M Channon In X Stefan Neubauer In X
Abstract:

Objectives

The purpose of this study was to assess vascular dysfunction in young smokers by high-resolution magnetic resonance imaging (MRI).

Background

Cigarette smoking is a well-known cause of endothelial dysfunction, reflected by impaired brachial artery reactivity to hyperemia. We hypothesized that smoking induces both peripheral endothelial dysfunction and altered function in central conduit arteries, and that these global changes in vascular function could be directly quantified in a single noninvasive examination using high-resolution MRI.

Methods

A total of 22 healthy young volunteers (mean age 31 +/- 2 years; 12 nonsmokers, 10 smokers: cumulative cigarette consumption 11.9 +/- 6.0 pack-years) underwent noninvasive high-resolution MRI to assess central vascular distensibility and pulse-wave velocity (PWV), and cross-sectional flow-mediated dilation (FMD) of the brachial artery.

Results

Brachial artery FMD was significantly reduced in smokers compared with nonsmokers (7.5 +/- 2.7% vs. 15.5 +/- 2.0%; p = 0.03), indicating impaired endothelium-dependant relaxation, whereas endothelium-independent responses to sublingual glyceroltrinitrate(400 mug) were identical in both groups. Impaired peripheral endothelial function in smokers was accompanied by striking decreases in central vascular distensibility in both the common carotid arteries (-45.7%; p = 0.02) and at multiple sites in the aorta (ascending aorta -26.9%, p = 0.04; thoracic descending aorta -25.0%, p = 0.01; abdominal descending aorta -25.5%, p = 0.02). Aortic arch PWV in smokers was increased by 19% (p = 0.02).

Conclusions

Cigarette smoking induces global changes in both peripheral and central vascular function. Direct quantification of multiple parameters of vascular function using high-resolution MRI will provide powerful new approaches to the assessment of vascular disease pathogenesis, diagnosis, and treatment.
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Functional changes in brain activity during acquisition and practice of movement sequences.

Issue 4 Vol 8 Published on 2004-10-01 PMID 15585904 PMCID N/A
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DOI: https://doi.org/10.1123/mcj.8.4.500
Authors: Hanneke I van Mier In X Joel S Perlmutter In X Steven E Petersen In X
Abstract: In the present study, brain activations were measured using positron emission tomography (PET) over the course of practice. Fourteen right-handed participants were scanned during six 1-min periods of practice tracing a cut-out maze design with their eyes closed. Practice-related decreases were found in the right premotor and posterior parietal cortex and left cerebellum, increases in the supplementary motor area (SMA) and primary motor cortex. The decrease in right premotor activity and the increase in SMA was significantly correlated with a decrease in the number of stops, implying involvement in learning and storing the movement sequence. The significant correlation between decreases in errors and left cerebellar and right posterior parietal activity suggests a role in accuracy. Involvement of the primary motor cortex in motor execution is suggested by the correlation of increased activation and movement speed. These results suggest that different neural structures (involving a premotor-parietal-cerebellar circuit) play a role in a sequential maze learning task.
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Value of delayed-enhancement cardiovascular magnetic resonance imaging in predicting myocardial viability after surgical revascularization.

Issue 12 Vol 110 Published on 2004-09-01 PMID 15353496 PMCID N/A
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DOI: https://doi.org/10.1161/01.cir.0000142045.22628.74
Authors: Joseph B Selvanayagam In X Attila Kardos In X Jane M Francis In X Frank Wiesmann In X Steffen E Petersen In X David P Taggart In X Stefan Neubauer In X
Abstract:

Background

Despite the accepted utility of delayed-enhancement MRI in identifying irreversible myocardial injury, no study has yet assessed its role as a viability tool exclusively in the setting of coronary artery bypass surgery (CABG), and no study has repeated delayed-enhancement MRI late after revascularization. In a clinical trial in which patients underwent CABG by either the off-pump or on-pump surgical technique, we hypothesized that (1) preoperative delayed-enhancement MRI would have high diagnostic accuracy in predicting viability and (2) the occurrence of perioperative myocardial necrosis would affect late regional wall motion recovery.

Methods and results

Fifty-two patients undergoing multivessel CABG were studied by preoperative and early (day 6) and late (6 months) postoperative cine MRI for global and regional functional assessment and delayed-enhancement MRI for assessment of irreversible myocardial injury. Preoperatively, 611 segments (21%) had abnormal regional function, whereas 421 segments (14%) showed evidence of hyperenhancement. At 6 months after revascularization, 57% (343 of 611) of dysfunctional segments improved contraction by at least 1 grade. When all preoperative dysfunctional segments were analyzed, there was a strong correlation between the transmural extent of hyperenhancement and the recovery in regional function at 6 months (P<0.001). Of a total of 96 previously dysfunctional but nonenhancing or minimally hyperenhancing myocardial segments that did not improve regional function at 6 months, 35 (36%) demonstrated new perioperative hyperenhancement in the early postoperative MRI scan.

Conclusions

Delayed-enhancement MRI is a powerful predictor of myocardial viability after surgery, suggesting an important role for this technique in clinical viability assessment.
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Comparison of sustained and transient activity in children and adults using a mixed blocked/event-related fMRI design.

Issue 2 Vol 22 Published on 2004-06-01 PMID 15193629 PMCID N/A
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DOI: https://doi.org/10.1016/j.neuroimage.2004.02.028
Authors: Kristin K Wenger In X Kristina M Visscher In X Francis M Miezin In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The ability to make direct comparisons between adult and child neuroimaging data is important to the study of the neural basis of cognitive development. Recent fMRI studies in adults have used mixed blocked/event-related designs to extract activity consistent with separable sustained, task-related processes and transient, trial-related processes. Because brain regions with different time courses of activity may have different roles in cognitive processing, the ability to distinguish between sustained and transient signals would contribute to understanding the functional roles of regions involved in cognitive processing. The developmental profile of such activity would give insight into how cognitive processing develops over time. The purpose of this study was to assess the utility of the mixed design to detect and dissociate sustained and transient activity in children, and to determine if the time courses or magnitudes of the extracted signals differ from those extracted from adults. An fMRI experiment was performed on 10 adults and 10 children (ages 7-8) using counterphase flickering checkerboard stimuli that produced sustained, transient, and a combination of sustained and transient responses in visual cortex. Analyses were performed using the general linear model (GLM) assuming a shape for sustained effects, but not for transient effects. In visual cortex, neither transient nor sustained effects showed significant between-group differences. For both groups, flickering checkerboard stimuli produced robust responses in visual cortex contralateral but not ipsilateral to the stimulus. Results extend the feasibility of direct statistical comparison of adults and children; mixed designs provide a means to examine neural activity in both adults and children related to sustained, task-level processes, likely related to task-level control.
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[Noonan's syndrome with an unusual combination of hypertrophic cardiomyopathy, congenital bicuspid aortic valve, coarctation of the aorta and hypoplastic aortic arch].

Issue 4 Vol 93 Published on 2004-04-01 PMID 15085376 PMCID N/A
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DOI: https://doi.org/10.1007/s00392-004-0051-y
Authors: S E Petersen In X O K Mohrs In X U Theile In X W Pohlmann In X T Voigtländer In X
Abstract: Noonan's syndrome is characterized by craniofacial anomalies, i. e. ptosis, webbing of the neck and a deep nuchal hairline, as well as skeletal deformities such as short stature, clinodactyly, pectus carinatum and funnel chest and other organ anomalies, mainly cardiac valve disease, less often testicular retention or kidney malformations. Noonan syndrome presents with aspects similar to Ullrich-Turner syndrome, but can be found in both male and female patients. In about one half of the patients with Noonan's syndrome cardiovascular anomalies occur, mostly anomalies of the right heart (mainly valvular pulmonary stenosis). Aortic stenosis and coarctation of the aorta are rarely seen. We report on a patient with four sequential potentially stenosing and stenosed parts of the proximal systemic circulation: hypertrophic cardiomyopathy, bicuspid aortic valve, coarctation of the aorta and a hypoplastic aortic arch as a part of Noonan's syndrome. This patient presents with a unique combination of anomalies, as he also shows a Madelung like deformity of the wrist.
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Accuracy of quantitative MR vessel wall imaging applying a semi-automated gradient detection algorithm--a validation study.

Issue 4 Vol 6 Published on 2004-01-01 PMID 15646893 PMCID N/A
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DOI: https://doi.org/10.1081/jcmr-200036198
Authors: Qian Wang In X Matthew D Robson In X Jane M Francis In X Steffen E Petersen In X Keith M Channon In X Stefan Neubauer In X Frank Wiesmann In X
Abstract:

Unlabelled

Magnetic resonance imaging (MRI) is uniquely suited to study the pathophysiology of arteriosclerosis. So far, magnetic resonance (MR) measurements of vessel dimensions have mainly been done by manual tracing of vessel wall contours. However, such data postprocessing is very time-consuming and has limited accuracy due to difficulties in precise tracing of the thin vessel wall.

Purpose

To assess the accuracy and reproducibility of quantitative vascular MR imaging applying a data analysis method based on (1) vessel wall unwrapping, followed by (2) a gradient detection algorithm for MR data postprocessing. Vascular MR imaging studies were done both in vessel phantoms and in healthy volunteers (n=29) on a clinical 1.5 T MR scanner. A dark blood double-inversion turbo spin echo sequence with fat suppression was applied, with proton-density-weighted and breath-hold acquisition for aortic imaging and T2-weighted acquisition for carotid imaging. Intraobserver and interobserver variability were systematically evaluated by two independent observers. A repeat study within 10 days of the first MRI was performed in 10 of these subjects for assessment of interstudy reproducibility.

Results

The semiautomated edge detection software revealed a clear view of the inner and outer vessel wall boundaries both in the phantoms and in the volunteers studied. There was close agreement between MR-derived measurements and phantom dimensions (mean difference of 1.1+/-16.9 mm2, 8.0+/-19.9 mm2, 9.0+/-12.1 mm2 for vessel wall cross-sectional area, inner vessel area, and total vessel area, respectively). Quantification of vessel dimensions was feasible in all 29 healthy volunteers studied. Semiautomated quantification of cross-sectional vessel wall area (mean+/-SD, 253.6+/-208.4 mm2) revealed close correlation for repeated measurements by one or two observers (r=0.99 each). Both intraobserver and interobserver variability of vessel wall area MR measurements were low (mean difference 7.5+/-16.7 mm2 and 14.4+/-24.6 mm2 , respectively). In the repeat study of 10 volunteers, MRI with semiautomated postprocessing quantitation revealed a high correlation and agreement of vessel dimensions between the two scans (r=0.994, mean difference 2.6+/-25.1 mm2).

Conclusion

Semiautomated analysis methods can provide approaches that benefit from the human understanding of the image and the computer's ability to measure precisely and rapidly. Thus, by combining the latest MRI methods and semiautomated image analysis methods, we are now able to reproducibly determine the geometric parameters of blood vessels.
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Anteroseptal or apical myocardial infarction: a controversy addressed using delayed enhancement cardiovascular magnetic resonance imaging.

Issue 3 Vol 6 Published on 2004-01-01 PMID 15347130 PMCID N/A
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DOI: https://doi.org/10.1081/jcmr-120038647
Authors: Joseph B Selvanayagam In X Attila Kardos In X Dermot Nicolson In X Jane Francis In X Steffen E Petersen In X Matthew Robson In X Adrian Banning In X Stefan Neubauer In X
Abstract:

Aim

Delayed enhancement MRI (DE-MRI) of the heart has been shown to reliably identify areas of irreversible myocardial damage. We sought to determine if the term anteroseptal MI is appropriate by correlating electrocardiographic, angiographic, cine MRI and DE-MRI findings.

Methods and results

Nineteen patients admitted to our hospital with their first acute anterior MI and whose ECG showed new Q waves in leads V1-V4 were studied. All patients underwent cardiac catheterization, cine MRI, and DE-MRI. The mean left ventricular ejection fraction was 53%+/-16%. All 19 patients had evidence of delayed hyperenhancement in one or more myocardial segments (mean number of affected segments 5.5+/-2.1). The mean mass of hyperenhanced myocardium was 14+/-8 grams, or 10%+/-6% of absolute LV mass. Nineteen (100%) and 15 (79%) patients showed evidence of delayed hyperenhancement of the apex and apical anterior segments respectively. Seven (37%) patients showed evidence of mid ventricular anteroseptal hyperenhancement and none had any hyperenhancement of basal anteroseptal segments.

Conclusion

High resolution cardiac MRI applied in patients with acute infarction and new Q waves in leads V1-V4 demonstrates the presence of predominantly apical, but not isolated septal or anteroseptal infarction.
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Effects of off-pump versus on-pump coronary surgery on reversible and irreversible myocardial injury: a randomized trial using cardiovascular magnetic resonance imaging and biochemical markers.

Issue 3 Vol 109 Published on 2004-01-01 PMID 14732755 PMCID N/A
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DOI: https://doi.org/10.1161/01.cir.0000109489.71945.bd
Authors: Joseph B Selvanayagam In X Steffen E Petersen In X Jane M Francis In X Matthew D Robson In X Attila Kardos In X Stefan Neubauer In X David P Taggart In X
Abstract:

Background

There is biochemical evidence that off-pump coronary artery bypass grafting (OPCABG) reduces myocardial injury compared with the use of cardiopulmonary bypass (ONCABG), but the functional significance of this is uncertain. We hypothesized that OPCABG surgery would result in reduced postoperative reversible (stunning) and irreversible myocardial injury, as assessed by cardiovascular MRI (CMRI).

Methods and results

In a single-center randomized trial, 60 patients undergoing multivessel total arterial revascularization were randomly assigned: 30 to OPCABG and 30 to ONCABG. Patients underwent preoperative and early postoperative cine MRI for assessment of global left ventricular function, and contrast-enhanced CMRI for assessment of irreversible myocardial injury. Serial troponin I measurements were obtained perioperatively and correlated with the CMRI findings. The mean preoperative cardiac index was similar in the 2 surgical groups (2.9+/-0.7 ONCABG; 2.9+/-0.8 OPCABG; P=0.9). After surgery, the cardiac index was significantly higher in the OPCABG group (2.7+/-0.6 ONCABG; 3.2+/-0.8 OPCABG; P=0.04). New irreversible myocardial injury was similar in incidence (36% ONCABG; 44% OPCABG; P=0.8) and magnitude (6.3+/-3.6 g ONCABG; 6.8+/-4.0 g OPCABG; P=0.9) across the 2 groups. The median area-under-the-curve (AUC) troponin I values were significantly larger in the ONCABG group (182 versus 135 microg/L; P=0.02). There was a moderate correlation between the troponin I AUC values and mean mass of new myocardial hyperenhancement (r(2)=0.4; P=0.008).

Conclusions

OPCABG results in significantly better left ventricular function early after surgery but does not reduce the incidence or extent of irreversible myocardial injury.
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Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging.

Issue 2 Vol 6 Published on 2004-01-01 PMID 15137338 PMCID N/A
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DOI: https://doi.org/10.1081/jcmr-120030581
Authors: Steffen E Petersen In X Oliver K Mohrs In X Georg Horstick In X Katja Oberholzer In X Nico Abegunewardene In X Kordula Ruetzel In X Joseph B Selvanayagam In X Matthew D Robson In X Stefan Neubauer In X Manfred Thelen In X Juergen Meyer In X Karl-Friedrich Kreitner In X
Abstract:

Background

Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses.

Methods

Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA injection [gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), 0.1 mmol/kg body weight = single dose] interrupted only for a complete stack of SA slices encompassing the entire left ventricle (LV) between minutes 20 and 28. Left ventricular mass showing hyperenhancement was determined. The measurement was repeated on the subsequent day with double dose CA (0.2 mmol/kg body weight). Differences of signal intensities for hyperenhanced, nonhyperenhanced myocardium, and LV cavity were calculated.

Results

Total mass of hyperenhancement from a complete SA stack acquired between minutes 20 and 28 was lower for single dose CA [9.0% vs. 14.2% for single and double dose, respectively (p = 0.03)]. Ten to 18 minutes after CA injection, there was no significant difference between the two doses and to an internal reference for both single and double dose. For single dose the image contrast between hyperenhancement and LV cavity was superior (minutes 10 to 16, p < 0.05) but inferior between hyperenhanced and nonhyperenhanced myocardium (minutes 6 to 16, p < 0.05).

Conclusion

Myocardial infarct size measurements are a function of time postcontrast when inversion time is held constant regardless of the contrast agent dose. These data underscore the fact that a standardized imaging protocol that defines how the appropriate inversion time should be selected is needed for comparison of results obtained at various cMR sites.
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[Cardio-MRT. The multimodal functional analysis of the future].

Issue N/A Vol 93 Suppl 4 Published on 2004-01-01 PMID 15085365 PMCID N/A
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DOI: https://doi.org/10.1007/s00392-004-1407-z
Authors: G Horstick In X S E Petersen In X T Voigtländer In X O K Mohrs In X W G Schreiber In X
Abstract: Since initial reports in the early 1990s cardiac magnetic resonance imaging (CMR) has matured and is likely to become an established method for routine cardiac diagnostics. The development of faster gradient-echo sequences and stronger magnetic fields has led to improved temporal and spatial resolution. Myocardial viability can be examined by morphological and functional analysis. Contrast enhanced MRI (ceMRI), perfusion measurements and regional wall motion analysis are the major diagnostic tools. The ability to image in arbitrary double oblique planes provides comprehensive visualization of the heart. The introduction of the MR navigator technique allowed for free-breathing motion corrected 3D coronary MR angiography with improved spatial resolution. Using this approach proximal and mid parts of the coronary arteries have been visualized. Subsequently, sensitivity and specificity for the detection of significant coronary stenoses has been evaluated in a multicenter trial demonstrating good sensitivity and specificity for the detection of significant left main and three vessel disease. However, specificity for the detection of single vessel disease was relatively low. Improved motion compensation techniques and novel imaging sequences (SSFP) are currently under investigation to further refine this technique. Despite these promising results coronary MR-angiography is not likely to replace conventional coronary angiography especially with regard to in-plane spatial resolution, coronary collateralization and in-stent restenosis. In contrast, coronary MR-angiography can provide useful morphological informations including functional analysis of the coronary vascular bed. The combination of a conventional cathlab with CMR may provide CMR-guided myocardial interventions. With further improvements in the catheter technology, CMR interventions using real-time imaging guidance will allow to take advantage of the excellent soft tissue contrast of CMR and the simultaneous visualization of the pulmonary, aortic and coronary vessels. CMR is advantageous for screening and follow-up examinations, and it offers comprehensive assessment of cardiac morphology and function in one single examination.
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Automated method for extracting response latencies of subject vocalizations in event-related fMRI experiments.

Issue 3 Vol 20 Published on 2003-11-01 PMID 14642496 PMCID N/A
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DOI: https://doi.org/10.1016/j.neuroimage.2003.07.020
Authors: J L Nelles In X H M Lugar In X R S Coalson In X F M Miezin In X S E Petersen In X B L Schlaggar In X
Abstract: For functional magnetic resonance imaging studies of the neural substrates of language, the ability to have subjects performing overt verbal responses while in the scanner environment is important for several reasons. Most directly, overt responses allow the investigator to measure the accuracy and reaction time of the behavior. One problem, however, is that magnetic resonance gradient noise obscures the audio recordings made of voice responses, making it difficult to discern subject responses and to calculate reaction times. ASSERT (Adaptive Spectral Subtraction for Extracting Response Times), an algorithm for removing MR gradient noise from audio recordings of subject responses, is described here. The signal processing improves intelligibility of the responses and also allows automated extraction of reaction times. The ASSERT-derived response times were comparable to manually measured times with a mean difference of -8.75 ms (standard deviation of difference = 26.2 ms). These results support the use of ASSERT for the purpose of extracting response latencies and scoring overt verbal responses.
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Images in cardiovascular medicine. Visualization of the ruptured plaque by magnetic resonance imaging.

Issue 20 Vol 108 Published on 2003-11-01 PMID 14623792 PMCID N/A
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DOI: https://doi.org/10.1161/01.cir.0000083603.61183.bb
Authors: Frank Wiesmann In X Matthew D Robson In X Jane Francis In X Steffen E Petersen In X C Paul Leeson In X Keith M Channon In X Stefan Neubauer In X
Abstract: No Abstract Available
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A 'broken heart' artifact in cardiovascular MR.

Issue 5 Vol 19 Published on 2003-10-01 PMID 14609195 PMCID N/A
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DOI: https://doi.org/10.1023/a:1025883613405
Authors: Steffen E Petersen In X Jane M Francis In X Frank Wiesmann In X Enrico Flossmann In X Matthew D Robson In X Stefan Neubauer In X
Abstract: No Abstract Available
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Diagnostic value of routine clinical parameters in acute myocardial infarction: a comparison to delayed contrast enhanced magnetic resonance imaging. Delayed enhancement and routine clinical parameters after myocardial infarction.

Issue 5 Vol 19 Published on 2003-10-01 PMID 14609190 PMCID N/A
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Keywords:
DOI: https://doi.org/10.1023/a:1025856816168
Authors: Steffen E Petersen In X Georg Horstick In X Thomas Voigtländer In X Karl-Friedrich Kreitner In X Thomas Wittlinger In X Steffen Ziegler In X Nico Abegunewardene In X Melanie Schmitt In X Wolfgang G Schreiber In X Peter Kalden In X Oliver K Mohrs In X Manfred Thelen In X Juergen Meyer In X
Abstract:

Aims

Contrast enhanced magnetic resonance imaging (ceMRI) has been shown to reliably identify irreversible myocardial injury. The aim of this study was to compare the findings on ceMRI with routine clinical markers of myocardial injury in patients with acute myocardial infarction (MI).

Methods and results

Twenty-four patients with acute MI were investigated at 1.5 T. The global myocardial function was analysed with a standard cine MR protocol and a stack of short axis slices encompassing the entire left ventricle. Corresponding short axis slices were acquired for delayed ceMRI 15-20 min after the administration of 0.2 mmol gadolinium-DTPA/kg body weight. Mass of hyperenhancement and peak creatine kinase release (peak CK) was determined for each patient. The presenting 12-lead ECG was analysed for ST-elevation on admission and later development of Q-waves. Mass of hyperenhancement correlated moderately well to peak CK (r = 0.65, p < 0.01) and endsystolic volume index (r = 0.55, p < 0.01). Mass of hyperenhancement was inversely correlated to ejection fraction (r = -0.50, p = 0.02). Neither the presence of ST elevation on the admission ECG nor the later development of Q-waves did relate to the transmural extent of hyperenhancement and to the mass of hyperenhancement.

Conclusion

Mass of hyperenhancement significantly correlates to global myocardial function and to peak CK. However, there is no relationship between the findings in ceMRI and 12-lead ECG abnormalities on admission suggesting an advantage of ceMRI in defining transmural extent and depicting small areas of necrosis.
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Functional-anatomic correlates of sustained and transient processing components engaged during controlled retrieval.

Issue 24 Vol 23 Published on 2003-09-01 PMID 13679414 PMCID PMC6740363
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DOI: https://doi.org/10.1523/jneurosci.23-24-08460.2003
Authors: Katerina Velanova In X Larry L Jacoby In X Mark E Wheeler In X Mark P McAvoy In X Steve E Petersen In X Randy L Buckner In X
Abstract: Controlled processing is central to episodic memory retrieval. In the present study, neural correlates of sustained, as well as transient, processing components were explored during controlled retrieval using a mixed blocked event-related functional magnetic resonance imaging paradigm. Results from 29 participants suggest that certain regions in prefrontal cortex, including anterior left inferior prefrontal cortex near Brodmann's Area (BA) 45/47 and more posterior and dorsal left prefrontal cortex near BA 44, increase activity on a trial-by-trial basis when high levels of control are required during retrieval. Providing direct evidence for control processes that participate on an ongoing basis, right frontal-polar cortex was strongly associated with a sustained temporal profile during high control retrieval conditions, as were several additional posterior regions, including those within left parietal cortex. These results provide evidence for functional dissociation within prefrontal cortex. Frontal-polar regions near BA 10 associate with temporally extended control processes that may underlie an attentional set, or retrieval mode, during controlled retrieval, whereas more posterior prefrontal regions associate with individual retrieval attempts. In particular, right frontal-polar cortex involvement in sustained processes reconciles a number of disparate findings that have arisen when contrasting blocked-trial paradigms with event-related paradigms.
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Mixed blocked/event-related designs separate transient and sustained activity in fMRI.

Issue 4 Vol 19 Published on 2003-08-01 PMID 12948724 PMCID N/A
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DOI: https://doi.org/10.1016/s1053-8119(03)00178-2
Authors: Kristina M Visscher In X Francis M Miezin In X James E Kelly In X Randy L Buckner In X David I Donaldson In X Mark P McAvoy In X Vidya M Bhalodia In X Steven E Petersen In X
Abstract: Recent functional magnetic resonance imaging (fMRI) studies using mixed blocked/event-related designs have shown activity consistent with separable sustained task-related processes and transient trial-related processes. In the mixed design, control blocks are intermixed with task blocks, during which trials are presented at varying intervals. Two studies were conducted to assess the ability of this design to detect and dissociate sustained task-related from transient trial-related activity. Analyses on both simulated and empirical data were performed by using the general linear model with a shape assumed for sustained effects, but not transient effects. In the first study, simulated data were produced with sustained time courses, transient time courses, and the sum of both together. Analyses of these data showed appropriate parsing of sustained and transient activity in all three cases. For the empirical fMRI experiment, counterphase-flickering checkerboard stimuli were constructed to produce sustained, transient, and combined sustained and transient responses in visual cortex. As with the simulation, appropriate parsing of sustained and transient activity was seen in all three cases; i.e., sustained stimuli produced sustained time courses and transient stimuli produced transient time courses. Combined stimuli produced both transient and sustained time courses. Critically, transient stimuli alone did not produce spurious positive sustained responses; sustained stimuli alone produced negligible spurious transient time courses. The results of these two studies along with supplemental simulations provide strong evidence that mixed designs are an effective tool for separating transient, trial-related activity from sustained activity in fMRI experiments. Mixed designs can allow researchers a means to examine brain activity associated with sustained processes, potentially related to task-level control signals.
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Late improvement of regional wall motion after the subacute phase of myocardial infarction treated by acute PTCA in a 6-month follow-up.

Issue 3 Vol 5 Published on 2003-07-01 PMID 12882079 PMCID N/A
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DOI: https://doi.org/10.1081/jcmr-120022264
Authors: S E Petersen In X T Voigtländer In X K F Kreitner In X G Horstick In X S Ziegler In X T Wittlinger In X N Abegunewardene In X M Schmitt In X W G Schreiber In X P Kalden In X O K Mohrs In X R Lippold In X M Thelen In X J Meyer In X
Abstract:

Background

The aim of this follow-up study was to investigate the late effects of acute coronary angioplasty (PTCA) on regional wall motion after the subacute phase of myocardial infarction (MI).

Methods and results

Seventeen patients were investigated initially at a median of 11 days and again at 6 months after acute PTCA for myocardial infarction (< 8 hours after onset of symptoms) by cardiac magnetic resonance imaging. Corresponding short-axis slices encompassing the left ventricle (LV) were acquired using a standard cine MR for regional wall motion analysis and using delayed contrast enhanced magnetic resonance imaging (ceMRI) for infarct size quantification. The infarct size was similar in the subacute phase and the 6 month follow-up (20.8 and 21.9%, respectively; n.s.). Regional wall motion improved significantly in the area of hyperenhancement [percentage wall thickening (PWT) 21.9% and 37.9%, p < 0.05] in contrast to remote normal myocardium (46.4% and 38.4%; n.s.). Regional wall motion was significantly poorer in transmural compared with nontransmural MI in the subacute stage, and a late improvement could only be observed in transmural MI.

Conclusion

Transmural areas of hyperenhancement displayed significant late long-term improvement of regional wall motion after acute PTCA, possibly related to prolonged stunning compared with nontransmural areas.
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Sustained and transient activity during an object-naming task: a mixed blocked and event-related fMRI study.

Issue 1 Vol 19 Published on 2003-05-01 PMID 12781725 PMCID N/A
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DOI: https://doi.org/10.1016/s1053-8119(03)00061-2
Authors: E Darcy Burgund In X Heather M Lugar In X Francis M Miezin In X Steven E Petersen In X
Abstract: Cognitive tasks often involve at least two types of processes-sustained processes potentially related to ongoing task demands and transient processes related to the processing of individual items within the task. Using functional magnetic resonance imaging, in conjunction with a mixed-blocked and event-related design, we examined sustained and transient patterns of neural activity during an object-naming task. Subjects were imaged during runs that alternated between control blocks and task blocks. During task blocks, primed and unprimed objects were intermixed and jittered in time. Regions of interest based on separate analyses of sustained and transient activities were tested independently for sustained and transient responses. Three general patterns of results were observed. (1) Some regions exhibited transient responses but little or no sustained response. These regions were widely distributed across the brain. (2) Other regions clearly exhibited both transient and sustained responses. These regions were found primarily in lateral and medial frontal lobes. (3) A few regions exhibited a sustained response but little or no transient responses. These regions were found in the basal ganglia, orbitofrontal lobe, and right lateral frontal lobe. Furthermore, two homotopic regional pairs in the right and left inferior frontal lobe (frontal operculum and inferior frontal cortex) showed a crossover of sustained and transient effects, with greater transient activity in the left and greater sustained activity in the right hemisphere. The asymmetric relationship between sustained and transient responses in prefrontal regions may be an example of task-specific biasing at work.
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Comparison of functional activation foci in children and adults using a common stereotactic space.

Issue 1 Vol 19 Published on 2003-05-01 PMID 12781724 PMCID N/A
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DOI: https://doi.org/10.1016/s1053-8119(03)00038-7
Authors: Hyunseon Christine Kang In X E Darcy Burgund In X Heather M Lugar In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The development of methods allowing direct comparisons between child and adult neuroimaging data is an important prerequisite for studying the neural bases of cognitive development. Several issues arise when attempting to make such direct comparisons, including the comparability of anatomical localization of functional responses and the magnitude and time course of the hemodynamic responses themselves. Previous results suggest that, after transformation into a common stereotactic space, anatomical differences between children (ages 7 and 8) and adults are small relative to the resolution of fMRI data. Here, we investigate whether time courses (BOLD responses) and locations of functional activation foci show similarities as well. Event-related fMRI was performed on 16 children (ages 7 and 8) and 16 adults, who pressed buttons in response to a visual stimulus. After transforming images into Talairach space, the coordinates of four consistent activations in each hemisphere were determined for each subject: two foci in the sensorimotor cortex, one focus in the visual cortex, and one focus in the supplementary motor area (eight activations in total). In seven foci, time courses were similar between children and adults, and peak amplitudes of time courses were comparable in all eight foci. There were negligible between-group differences in location of all foci. Variability of activation location was statistically similar in the two groups. In voxelwise group comparison images, minimal differences were found between children and adults in visual and motor cortex regions. The small differences in time courses and locations of activation foci between child and adult brains validate the feasibility of direct statistical comparison of these groups within a common space.
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A procedure for identifying regions preferentially activated by attention to semantic and phonological relations using functional magnetic resonance imaging.

Issue 3 Vol 41 Published on 2003-01-01 PMID 12457755 PMCID N/A
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DOI: https://doi.org/10.1016/s0028-3932(02)00162-8
Authors: Kathleen B McDermott In X Steven E Petersen In X Jason M Watson In X Jeffrey G Ojemann In X
Abstract: A procedure is introduced for using functional magnetic resonance imaging (fMRI) techniques to identify neural regions associated with attention to semantic and phonological aspects of written words within a single group of subjects. Short lists (16 words/list), consisting of visually-presented semantically-related words (bed, rest) or rhyming words (weep, beep) were presented rapidly to subjects, who were asked to attend to the relations among the words. Regions preferentially involved in attention to semantic relations appeared within left anterior/ventral inferior frontal gyrus (IFG, approximate Brodmann Area, BA47), left posterior/dorsal IFG (BA44/45), left superior/middle temporal cortex (BA22/21), left fusiform gyrus (BA37), and right cerebellum. Regions preferentially involved in attention to phonological relations appeared within left inferior frontal cortex (near BA6/44, posterior to the semantic regions within IFG described above) and within bilateral inferior parietal cortex (BA40) and precuneus (BA7). This method is notable in that a comparison of the two tasks within some of the individual subjects revealed activation patterns similar to the group average, especially within left inferior frontal and left superior/middle parietal cortices. This fact combined with the efficiency with which the data can be obtained (here, in about an hour of functional scanning) and the adaptability of the task for many different subject populations suggests a wide range of possibilities for this technique: it could be used to track language development (e.g. in children), compare language organization across subject populations (e.g. for dyslexic or blind subjects), and identify language regions within individuals (e.g. potentially to aid in surgical planning).
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Role of the cerebellum in motor cognition.

Issue N/A Vol 978 Published on 2002-12-01 PMID 12582064 PMCID N/A
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DOI: https://doi.org/10.1111/j.1749-6632.2002.tb07578.x
Authors: Hanneke I Van Mier In X Steve E Petersen In X
Abstract: Cerebellar data from five experiments using different groups of subjects performing the same motor learning task are presented. Positron emission tomography (PET) as well as functional magnetic resonance imaging (fMRI) was used to study changes in cerebellar activations as an effect of learning. Cerebellar brain activations obtained during the performance of a new motor task were compared to activations during the performance of the same task after as well as during practice. To account for changes in velocity and somatosensory processing as an effect of practice, two control conditions were included. Behavioral data showed that as an effect of practice performance speed as well as accuracy increased in all five experiments and groups. Neuroimaging data from adults as well as children showed differential changes in brain activations in different cerebellar areas. In all experiments an area in the left lateral cerebellum showed practice-related decreases, which were most likely related to a decrease in errors. In two experiments a highly significant correlation was found between the decrease in errors and the decrease in left cerebellar activation. An area in the right lateral cerebellum and one in the ipsilateral anterior vermis showed activations that seemed related to the level of capacity at which the subjects were performing and might refer to timing-related aspects of the task.
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Role of the posterolateral cerebellum in language.

Issue N/A Vol 978 Published on 2002-12-01 PMID 12582063 PMCID N/A
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DOI: https://doi.org/10.1111/j.1749-6632.2002.tb07577.x
Authors: Andrea L Gebhart In X Steven E Petersen In X W T Thach In X
Abstract: Historically, scientists have believed that the cerebellum controls only movement. However, recent evidence from neuroimaging and human lesion studies suggests that the right posterolateral cerebellar hemisphere is involved, independently of movement, in helping an individual to generate verbs for given nouns. We sought to elucidate the key factors contributing to the verb generation deficits of subjects with right posterolateral cerebellar damage and thus to better understand the specific contributions of the postero-lateral cerebellum to language. We compared the performance of subjects with focal left-sided posterolateral cerebellar lesions, those with focal right-sided posterolateral cerebellar lesions, and neurologically normal pilot control subjects on an antonym generation task, noun (category member) generation task, verb selection task, and lexical decision task. Preliminary results show that subjects with right cerebellar lesions are impaired relative to other subjects only on the antonym generation task. The results provide evidence that the right cerebellar language deficit is not due solely to deficits in "mental movement" coupled to a verb and that internal generation of a word seems to be a key factor in eliciting a deficit. In addition, a semantic processing demand may be necessary but insufficient to elicit a right cerebellar language deficit. The results support the theory that the right posterolateral cerebellar hemisphere assists the left cerebral hemisphere in helping an individual learn to generate specific types of spoken, two-word associations. The full nature of this process awaits further investigation.
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The feasibility of a common stereotactic space for children and adults in fMRI studies of development.

Issue 1 Vol 17 Published on 2002-09-01 PMID 12482076 PMCID N/A
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DOI: https://doi.org/10.1006/nimg.2002.1174
Authors: E Darcy Burgund In X Hyunseon Christine Kang In X James E Kelly In X Randy L Buckner In X Abraham Z Snyder In X Steven E Petersen In X Bradley L Schlaggar In X
Abstract: The question of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7-8 years of age) and 20 young adults (18-30 years of age) were transformed to a common space. Overall brain shape was assessed by tracing the outer boundaries of the brains in three orientations, and more local anatomy was assessed by analysis of portions of 10 selected sulci. Small, but consistent, differences in location and variability were observed in specific locations of the sulcal tracings and outer-boundary sections. In Study 2, a computer simulation was used to assess the extent to which the small anatomical differences observed in Study 1 would produce spurious effects in functional imaging data. Results indicate that, assuming a functional resolution of 5 mm in images averaged across subjects, anatomical differences in either variability or location between children and adults of the magnitude obperved in Study 1 would not negatively affect functional image comparisons. We conclude that atlas-transformed brain morphology is relatively consistent between 7- and 8-year-old children and adults at a resolution appropriate to current functional imaging and that the small anatomical differences present do not limit the usefulness of comparing child and adult functional images within a common stereotactic space.
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Word retrieval learning modulates right frontal cortex in patients with left frontal damage.

Issue 1 Vol 36 Published on 2002-09-01 PMID 12367514 PMCID N/A
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DOI: https://doi.org/10.1016/s0896-6273(02)00936-4
Authors: Valeria Blasi In X Alexis C Young In X Aaron P Tansy In X Steven E Petersen In X Abraham Z Snyder In X Maurizio Corbetta In X
Abstract: Previous studies have suggested that recovery or compensation of language function after a lesion in the left hemisphere may depend on mechanisms in the right hemisphere. However, a direct relationship between performance and right hemisphere activity has not been established. Here, we show that patients with left frontal lesions and partially recovered aphasia learn, at a normal rate, a novel word retrieval task that requires the damaged cortex. Verbal learning is accompanied by specific response decrements in right frontal and right occipital cortex, strongly supporting the compensatory role of the right hemisphere. Furthermore, responses in left occipital cortex are abnormal and not modulated by practice. These findings indicate that frontal cortex is a source of top-down signals during learning.
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Reactivation of networks involved in preparatory states.

Issue 6 Vol 12 Published on 2002-06-01 PMID 12003859 PMCID N/A
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DOI: https://doi.org/10.1093/cercor/12.6.590
Authors: Gordon L Shulman In X Aaron P Tansy In X Michelle Kincade In X Steven E Petersen In X Mark P McAvoy In X Maurizio Corbetta In X
Abstract: We report an endogenous signal that has a widespread cortical distribution and is time-locked to the termination of a sustained state of task-readiness. In three event-related functional magnetic resonance imaging (fMRI) experiments, subjects saw an arrow cue that predicted either the direction of motion or the location of a subsequent test stimulus. A reactivation of the BOLD (blood oxygenation level-dependent) signal occurred at the termination of the state of readiness in occipital regions that were transiently activated by the cue and in frontal-parietal regions that maintained an attentional set over the trial. Moreover, a delayed activation occurred in prefrontal and temporo-parietal regions that did not initially respond to the cue and that have been implicated in re-orienting attention to novel sensory events. These latter regions may have generated control signals that ended the state of readiness in regions active during the cue period. These results indicate that terminating a state of readiness produces a widely distributed cortical signal and suggest that areas involved in a preparatory state may be maintained as a network which can be modulated as a whole.
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Functional neuroanatomical differences between adults and school-age children in the processing of single words.

Issue 5572 Vol 296 Published on 2002-05-01 PMID 12029136 PMCID N/A
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DOI: https://doi.org/10.1126/science.1069464
Authors: Bradley L Schlaggar In X Timothy T Brown In X Heather M Lugar In X Kristina M Visscher In X Francis M Miezin In X Steven E Petersen In X
Abstract: A critical issue in developmental cognitive neuroscience is the extent to which the functional neuroanatomy underlying task performance differs in adults and children. Direct comparisons of brain activation in the left frontal and extrastriate cortex were made in adults and children (aged 7 to 10 years) performing single-word processing tasks with visual presentation; differences were found in circumscribed frontal and extrastriate regions. Conceivably, these differences could be attributable exclusively to performance discrepancies; alternatively, maturational differences in functional neuroanatomy could exist despite similar performance. Some of the brain regions examined showed differences attributable to age independent of performance, suggesting that maturation of the pattern of regional activations for these tasks is incomplete at age 10.
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Measurements of cortical interstitium in biopsies from human kidney grafts: how representative and how reproducible?

Issue 5 Vol 17 Published on 2002-05-01 PMID 11981064 PMCID N/A
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DOI: https://doi.org/10.1093/ndt/17.5.788
Authors: Anne Ringer Ellingsen In X Jens Randel Nyengaard In X Ruth Østerby In X Kaj Anker Jørgensen In X Steffen Ellebaek Petersen In X Niels Marcussen In X
Abstract:

Background

The aim of the study was to evaluate how well a biopsy from one region of a human renal allograft represented biopsies from other regions regarding the renal interstitial tissue assessed by stereology. Furthermore, we wanted to evaluate the reproducibility of the measurements.

Methods

Punch biopsies (3 mm) from six regions in each kidney were obtained from seven explanted renal grafts with varying degrees of clinically diagnosed chronic and acute rejection. One kidney, removed for a minor pelvic tumour, served as reference material. Using point counting on PAS-stained sections, the volume fraction of the interstitial tissue per glomerular cortex V(V)(interstitium/cortex) was estimated. From each kidney, two of the six biopsies were re-evaluated by the same observer.

Results

V(V)(interstitium/cortex) varied from 0.25 to 0.78 between the explanted kidneys vs 0.26 in the reference kidney. Variations within the kidneys were low, expressed by standard deviations (SD) of between 0.04 and 0.06, and coefficients of variation (CV) between 0.06 and 0.22. The SD estimated from repeated measurements was 0.04 and CV was 0.07.

Conclusions

Biopsies from one region of the kidney were found to be representative for estimates of interstitial tissue in explanted human kidney grafts, and the degree of reproducibility was high when using point counting, as in the present study.
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Quantification of shunt volumes in congenital heart diseases using a breath-hold MR phase contrast technique--comparison with oximetry.

Issue 1 Vol 18 Published on 2002-02-01 PMID 12135123 PMCID N/A
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DOI: https://doi.org/10.1023/a:1014394626363
Authors: Steffen E Petersen In X Thomas Voigtländer In X Karl-Friedrich Kreitner In X Peter Kalden In X Thomas Wittlinger In X Jürgen Scharhag In X Georg Horstick In X Dietmar Becker In X Gerhard Hommel In X Manfred Thelen In X Jürgen Meyer In X
Abstract:

Aims

Comparison of breath-hold MR phase contrast technique in the estimation of cardiac shunt volumes with the invasive oximetric technique.

Methods and results

Seventeen patients with various cardiac shunts (10 ASD, 3 VSD, 1 PDA, 3 PFO) and five healthy volunteers were investigated using a 1.5 Tesla system. The mean flow velocity, the mean volume flow and the transverse area in the ascending aorta and the left and right pulmonary artery were measured using the MR phase contrast breath-hold technique (through plane, FLASH 2D-sequence, TR/TE 11/5 ms, phase length 106 ms, VENC 250 cm/s). The ratio of mean flow in the pulmonary (Qp: sum of mean flows in the left and right pulmonary arteries) and the systemic circulation (Qs: mean flow in the ascending aorta) was calculated and compared with invasively measured Qp:Qs ratios. Oximetry was performed within 24 h of the MR investigation. The non-invasive shunt measurement in the 17 patients showed a mean Qp:Qs ratio of 2.00 +/- 0.86. Comparing the MR data with the invasively measured Qp:Qs showed a correlation coefficient of r = 0.91 (p < 0.001).

Conclusion

Cardiac shunt volumes can be measured reliably using a shorter acquisition time with breath-hold MR phase contrast technique.
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[Evaluation of myocardial perfusion reserve in patients with CAD using contrast-enhanced MRI: a comparison between semiquantitative and quantitative methods].

Issue 2 Vol 174 Published on 2002-02-01 PMID 11898081 PMCID N/A
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DOI: https://doi.org/10.1055/s-2002-20109
Authors: M Schmitt In X O K Mohrs In X S E Petersen In X K F Kreitner In X T Voigtländer In X T Wittlinger In X G Horstick In X S Ziegler In X J Meyer In X M Thelen In X W G Schreiber In X
Abstract:

Objective

Comparison between two semiquantitative methods and a quantitative evaluation of myocardial blood flow (MBF) for assessment of myocardial perfusion reserve (MPR) in patients with CAD.

Material and methods

9 patients with coronary stenoses > 50 % were examined with an ECG-gated Saturation Recovery Turbo FLASH sequence by using Gd-DTPA as contrast agent (CA). The entive measurements were performed both during rest and hyperemia induced by adenosine. The up-slopes of the signal-time S(t) curves in the myocardium and left ventricular (LV) cavity were evaluated by a linear fit. MPR was calculated from the original up-slopes of the myocardial S(t) curves and from the up-slopes, which were normalized to the up-slopes of the LV S(t) curves, respectively. For quantification of MBF values, the mathematical model MMID 4 was used and MPR was evaluated from the MBF values.

Results

With all tested methods, MPR was reduced in myocardial regions subtended by arteries with stenoses >/= 70 % compared with remote regions. With MMID 4 and the normalized up-slope method, differences between severe ischemic and remote regions were statistically significant.

Conclusion

The up-slope method with normalization and quantification with MMID 4 are more sensitive methods to differentiate between remote and ischemic myocardium than the up-slope method without normalization.
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Wada testing reveals frontal lateralization for the memorization of words and faces.

Issue 1 Vol 14 Published on 2002-01-01 PMID 11798392 PMCID N/A
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DOI: https://doi.org/10.1162/089892902317205375
Authors: W M Kelley In X J G Ojemann In X R D Wetzel In X C P Derdeyn In X C J Moran In X D T Cross In X J L Dowling In X J W Miller In X S E Petersen In X
Abstract: Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.
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Dissociating memory retrieval processes using fMRI: evidence that priming does not support recognition memory.

Issue 6 Vol 31 Published on 2001-09-01 PMID 11580903 PMCID N/A
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DOI: https://doi.org/10.1016/s0896-6273(01)00429-9
Authors: D I Donaldson In X S E Petersen In X R L Buckner In X
Abstract: We employed event-related fMRI to constrain cognitive accounts of memory retrieval. Studies of explicit retrieval reveal that lateral and medial parietal, dorsal middle frontal gyrus, and anterior prefrontal cortex respond more for studied than new words, reflecting a correlate of "retrieval success." Studies of implicit memory suggest left temporal cortex, ventral and dorsal inferior frontal gyrus respond less for studied than new words, reflecting a correlate of "conceptual priming." In the present study, responses for old and new items were compared during performance on explicit recognition (old/new judgement) and semantic (abstract/concrete judgement) tasks. Regions associated with priming were only modulated during the semantic task, whereas regions associated with retrieval success were modulated during both tasks. These findings constrain functional-anatomic accounts of the networks, suggesting that processes associated with priming do not support explicit recognition judgments.
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Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing.

Issue 6 Vol 13 Published on 2001-08-01 PMID 11564326 PMCID N/A
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DOI: https://doi.org/10.1162/08989290152541485
Authors: A L Roskies In X J A Fiez In X D A Balota In X M E Raichle In X S E Petersen In X
Abstract: To distinguish areas involved in the processing of word meaning (semantics) from other regions involved in lexical processing more generally, subjects were scanned with positron emission tomography (PET) while performing lexical tasks, three of which required varying degrees of semantic analysis and one that required phonological analysis. Three closely apposed regions in the left inferior frontal cortex and one in the right cerebellum were significantly active above baseline in the semantic tasks, but not in the nonsemantic task. The activity in two of the frontal regions was modulated by the difficulty of the semantic judgment. Other regions, including some in the left temporal cortex and the cerebellum, were active across all four language tasks. Thus, in addition to a number of regions known to be active during language processing, regions in the left inferior frontal cortex were specifically recruited during semantic processing in a task-dependent manner. A region in the right cerebellum may be functionally related to those in the left inferior frontal cortex. Discussion focuses on the implications of these results for current views regarding neural substrates of semantic processing.
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An event-related fMRI study of overt and covert word stem completion.

Issue 1 Pt 1 Vol 14 Published on 2001-07-01 PMID 11525327 PMCID N/A
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DOI: https://doi.org/10.1006/nimg.2001.0779
Authors: E D Palmer In X H J Rosen In X J G Ojemann In X R L Buckner In X W M Kelley In X S E Petersen In X
Abstract: In fMRI studies of language processing, it would be extremely useful to obtain high-quality images during tasks requiring spoken output. Recent studies have suggested that this may be possible, particularly if event-related fMRI methods are used. This study assesses the feasibility of acquiring interpretable images during speech by applying event-related methods to visual word stem completion, a task that has been studied extensively. On each trial, a different three-letter word stem (e.g., COU) was presented visually and subjects were required to generate a word beginning with that stem (e.g., COUSIN). In covert runs, subjects were instructed to say the word once to themselves, without moving their lips. In overt runs, subjects were instructed to say the word once aloud. Ten subjects were scanned during six overt runs and six covert runs at three presentation rates. Data were analyzed using an implementation of the general linear model making no assumptions about response shape. Images were relatively free of artifacts, and regions demonstrating task-related activation were similar to those reported in previous imaging studies. Regions active during overt task performance were similar to those active during covert task performance, with the addition of several regions commonly associated with motor aspects of speech production. Consistent with other studies, magnitude of activation was greater in the overt condition than in the covert condition, and there was a modest decrease in magnitude at the fastest presentation rate. Together, these results help to validate the use of event-related fMRI during tasks that require spoken output. Press
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Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks.

Issue 1 Pt 1 Vol 14 Published on 2001-07-01 PMID 11525336 PMCID N/A
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DOI: https://doi.org/10.1006/nimg.2001.0791
Authors: T S Braver In X D M Barch In X W M Kelley In X R L Buckner In X N J Cohen In X F M Miezin In X A Z Snyder In X J M Ollinger In X E Akbudak In X T E Conturo In X S E Petersen In X
Abstract: Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).
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Dissociating state and item components of recognition memory using fMRI.

Issue 1 Vol 13 Published on 2001-01-01 PMID 11133316 PMCID N/A
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DOI: https://doi.org/10.1006/nimg.2000.0664
Authors: D I Donaldson In X S E Petersen In X J M Ollinger In X R L Buckner In X
Abstract: Cognitive functions such as memory retrieval involve a combination of state- and item-related processes. State-related processes are sustained throughout a task (e.g., "retrieval mode" associated with ongoing goals), whereas item-related processes are transient and allied to individual stimuli (e.g., "retrieval success" associated with the recovery of information from memory). The present study employed a mixed "blocked and event-related" experimental design to identify neural mechanisms that support state- and item-related processes during a recognition memory task. Subjects alternated between blocks of fixation and recognition memory (discriminating between old and new words). Critically, event-related procedures were embedded within the recognition blocks, including the jittering of sequential trials. This design ensures that the temporal profiles of state- and item-related activity differ and consequently renders them separable; without this procedure item-related activity would summate to produce a state-like response. Results suggest three classes of brain region support recognition memory, exhibiting: (1) predominantly transient activity (including regions in medial parietal, lateral parietal, and anterior left frontal cortex) reflecting item-related processing associated with "retrieval success," (2) predominantly sustained activity (including decreased activity in bilateral parahippocampal cortex) reflecting state-related processing associated with "retrieval mode," (3) concurrent sustained and transient activity (including regions in left middle frontal gyrus, bilateral frontal operculum, and medial frontal gyrus), reflecting a combination of state- and item-related processing. The present findings support the idea that recognition memory tasks are dependent upon a combination of state- and item-related processes that have dissociable neural correlates identifiable using fMRI. Moreover, the mixed "blocked and event-related" design employed here provides a general procedure for separating state- and item-related processes.
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Multiple neural correlates of detection in the human brain.

Issue 1 Vol 98 Published on 2001-01-01 PMID 11134528 PMCID PMC14587
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DOI: https://doi.org/10.1073/pnas.98.1.313
Authors: G L Shulman In X J M Ollinger In X M Linenweber In X S E Petersen In X M Corbetta In X
Abstract: We used event-related functional MRI to examine the neural consequences of detecting the presence or absence of a stimulus. Subjects detected a brief interval of coherent motion embedded in dynamic noise that was presented throughout a test period. Several brain regions, including V1/V2, middle temporal complex (MT+), left intraparietal cortex, and the frontal eye field, were activated at the onset of the dynamic noise, irrespective of whether a coherent motion target was presented early or late in the test period, or not at all. These regions, many of which were motion sensitive, were likely involved in searching for and detecting the target. The blood oxygenation level-dependent signal in these regions was higher in trials in which a target was detected than in trials in which it was missed or not presented, indicating that these regions were modulated by detection. Moreover, the blood oxygenation leveldependent signal in these regions decayed quickly once a target was detected, even though the dynamic noise continued to be displayed, indicating that they were shut down after detection. Therefore, detection-related modulations occurred in the same regions that accumulate target information over time, in agreement with current psychological and neural models of detection. Many other regions, however, including areas in prefrontal cortex and anterior cingulate, were not involved in searching for a target. In these regions, activation began early in the test period when an early target was detected but began late in the test period when a late target was detected or when a response was correctly withheld in the absence of a motion target. The signal in these regions was therefore triggered by a discrete event during the test interval that was related to presence-absence detection.
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Neural correlates of recovery from aphasia after damage to left inferior frontal cortex.

Issue 12 Vol 55 Published on 2000-12-01 PMID 11134389 PMCID N/A
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DOI: https://doi.org/10.1212/wnl.55.12.1883
Authors: H J Rosen In X S E Petersen In X M R Linenweber In X A Z Snyder In X D A White In X L Chapman In X A W Dromerick In X J A Fiez In X M D Corbetta In X
Abstract:

Objective

To determine neural correlates of recovery from aphasia after left frontal injury.

Methods

The authors studied the verbal performance of patients with infarcts centered in the left inferior frontal gyrus (IFG), using a battery of attention-demanding lexical tasks that normally activate the left IFG and a simpler reading task that does not normally recruit the left IFG. The authors used positron emission tomography (PET) and functional MRI (fMRI) to record neural activity in the same group of patients during word-stem completion, one of the attention-demanding lexical tasks. To identify potential neural correlates of compensation/recovery, they analyzed the resulting data for the group as a whole (PET, fMRI) and also for each participant (fMRI).

Results

Patients with damage to the left IFG were impaired on all attention-demanding lexical tasks, but they completed the word-reading tasks normally. The imaging studies demonstrated a stronger-than-normal response in the right IFG, a region homologous to the damaged left IFG. The level of activation in the right IFG did not correlate with verbal performance, however. In addition, a perilesional response within the damaged left IFG was localized in the two patients who gave the best performance in the word-stem completion task and showed the most complete recovery from aphasia.

Conclusions

Right-IFG activity may represent either the recruitment of a preexisting neural pathway through alternative behavioral strategies or an anomalous response caused by removal of the left IFG. Perilesional activity in the left IFG may represent sparing or restoration of normal function in peri-infarctual tissue that was inactive early on after injury. This activity may be of greater functional significance than right IFG activity because it was associated with more normal verbal performance.
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Retrieval success is accompanied by enhanced activation in anterior prefrontal cortex during recognition memory: an event-related fMRI study.

Issue 6 Vol 12 Published on 2000-11-01 PMID 11177417 PMCID N/A
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DOI: https://doi.org/10.1162/08989290051137503
Authors: K B McDermott In X T C Jones In X S E Petersen In X S K Lageman In X H L Roediger In X
Abstract: Neural regions associated with retrieval success were identified using event-related fMRI procedures and randomly ordered trials on a recognition memory test. Differences between hits and correct rejections (CRs) occurred multiple regions, including bilateral anterior and right dorsolateral prefrontal cortex, bilateral inferior parietal cortex, and right superior parietal cortex (all hits > CRs), and right occipital cortex (CRs > hits). The hit > CR pattern is not compromised by time-on-task explanations because response latencies for correctly rejected words exceeded those for hits. Converging evidence for the claim that the hit > CR pattern identified neural correlates of retrieval success was obtained by unconfounding item history and retrieval success. That is, we implemented a third condition in which nonstudied words were presented, yet retrieval success was hypothesized to facilitate CRs of these lures. Specifically, in when confronted with a familiar, yet nonstudied word, (e.g., nosedive after studying nosebleed and skydive), subjects might adopt a strategy whereby they recall the studied word(s) that gave rise to the familiarity (nosebleed, skydive) and thereby reject the lure. This method of instantiating retrieval success under conditions in which the target word had not been studied offers converging evidence for the claim that anterior-prefrontal cortex (among other regions) demonstrates enhanced activation during retrieval success.
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Memory's echo: vivid remembering reactivates sensory-specific cortex.

Issue 20 Vol 97 Published on 2000-09-01 PMID 11005879 PMCID PMC27159
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DOI: https://doi.org/10.1073/pnas.97.20.11125
Authors: M E Wheeler In X S E Petersen In X R L Buckner In X
Abstract: A fundamental question in human memory is how the brain represents sensory-specific information during the process of retrieval. One hypothesis is that regions of sensory cortex are reactivated during retrieval of sensory-specific information (1). Here we report findings from a study in which subjects learned a set of picture and sound items and were then given a recall test during which they vividly remembered the items while imaged by using event-related functional MRI. Regions of visual and auditory cortex were activated differentially during retrieval of pictures and sounds, respectively. Furthermore, the regions activated during the recall test comprised a subset of those activated during a separate perception task in which subjects actually viewed pictures and heard sounds. Regions activated during the recall test were found to be represented more in late than in early visual and auditory cortex. Therefore, results indicate that retrieval of vivid visual and auditory information can be associated with a reactivation of some of the same sensory regions that were activated during perception of those items.
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Solid-state 13 C and 31 P NMR analysis of urinary stones.

Issue 3 Pt 1 Vol 164 Published on 2000-09-01 PMID 10953168 PMCID N/A
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DOI: https://doi.org/10.1097/00005392-200009010-00062
Authors: M Bak In X J K Thomsen In X H J Jakobsen In X S E Petersen In X T E Petersen In X N C Nielsen In X
Abstract:

Purpose

We investigated the applicability of solid-state nuclear magnetic resonance (NMR) spectroscopy to obtain information about the structure and composition of renal calculi.

Materials and methods

Various types urinary and bladder stones as well as a variety of presumed constituents were investigated using 13C and 31P magic-angle spinning (MAS) solid-state NMR. Different experimental methods were applied to differentiate resonances from crystalline/amorphous (immobile/mobile) as well as protonated/non-protonated moieties. The NMR spectra were analyzed using multiple-component numerical simulations and iterative fitting to identify and quantify the major amorphous or crystalline organic and inorganic components.

Results

By comparison of the NMR spectra for the various renal calculi with those obtained under similar conditions for various presumed components, it is demonstrated possible to unambiguously distinguish and quantify the major amorphous or crystalline organic and inorganic components. The components are identified in terms of their isotropic and anisotropic chemical shielding parameters, protonation or proximity of protons, and the degree of crystallinity/mobility. For the calculi investigated we have detected and quantified calcium oxalate, uric acid, struvite, and calcium phosphates that closely resemble brushite and calcium hydroxyapatite.

Conclusions

Using 13C and 31P MAS NMR spectroscopy we have been able to account for 60 to 85% (by weight) of the constituents in the calculi investigated. The ability to identify and quantify both crystalline and amorphous components makes solid-state NMR an interesting new method for the compositional analysis of renal calculi.
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Characterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timing.

Issue 6 Pt 1 Vol 11 Published on 2000-06-01 PMID 10860799 PMCID N/A
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DOI: https://doi.org/10.1006/nimg.2000.0568
Authors: F M Miezin In X L Maccotta In X J M Ollinger In X S E Petersen In X R L Buckner In X
Abstract: Rapid-presentation event-related functional MRI (ER-fMRI) allows neuroimaging methods based on hemodynamics to employ behavioral task paradigms typical of cognitive settings. However, the sluggishness of the hemodynamic response and its variance provide constraints on how ER-fMRI can be applied. In a series of two studies, estimates of the hemodynamic response in or near the primary visual and motor cortices were compared across various paradigms and sampling procedures to determine the limits of ER-fMRI procedures and, more generally, to describe the behavior of the hemodynamic response. The temporal profile of the hemodynamic response was estimated across overlapping events by solving a set of linear equations within the general linear model. No assumptions about the shape were made in solving the equations. Following estimation of the temporal profile, the amplitude and timing were modeled using a gamma function. Results indicated that (1) within a region, for a given subject, estimation of the hemodynamic response is extremely stable for both amplitude (r(2) = 0.98) and time to peak (r(2) = 0.95), from one series of measurements to the next, and slightly less stable for estimation of time to onset (r(2) = 0.60). (2) As the trial presentation rate changed (from those spaced 20 s apart to temporally overlapping trials), the hemodynamic response amplitude showed a small, but significant, decrease. Trial onsets spaced (on average) 5 s apart showed a 17-25% reduction in amplitude compared to those spaced 20 s apart. Power analysis indicated that the increased number of trials at fast rates outweighs this decrease in amplitude if statistically reliable response detection is the goal. (3) Knowledge of the amplitude and timing of the hemodynamic response in one region failed to predict those properties in another region, even for within-subject comparisons. (4) Across subjects, the amplitude of the response showed no significant correlation with timing of the response, for either time-to-onset or time-to-peak estimates. (5) The within-region stability of the response was sufficient to allow offsets in the timing of the response to be detected that were under a second, placing event-related fMRI methods in a position to answer questions about the change in relative timing between regions.
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Obesity and physical and emotional well-being: associations between body mass index, chronic illness, and the physical and mental components of the SF-36 questionnaire.

Issue 2 Vol 8 Published on 2000-03-01 PMID 10757202 PMCID N/A
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DOI: https://doi.org/10.1038/oby.2000.17
Authors: H A Doll In X S E Petersen In X S L Stewart-Brown In X
Abstract:

Objective

To clarify the associations between obesity and health-related quality of life by exploring the associations between physical and emotional well-being in relation to obesity and the presence of other chronic illness.

Research methods and procedures

The study data were collected as part of a postal-survey within the old Oxford Regional Health Authority of England in 1997. Completed questionnaires were returned by 8889 of 13,800 randomly selected adults aged 18 to 64 years. The main outcome measures were body mass index in five categories (underweight, normal weight, overweight, moderately obese, morbidly obese); chronic illness status (any vs. none and number of such illnesses 0, 1 to 2, 3+); and mean SF-36 questionnaire score in two summary component measures reflecting physical and emotional well-being.

Results

Of the subjects, 31% were overweight and an additional 11% were obese. Body mass index was significantly associated with health status, but the pattern varied according to whether the measure reflected physical or emotional well-being. Physical, but not emotional, well-being deteriorated markedly with increasing degree of overweight and was limited in subjects who were obese but had no other chronic condition; subjects with chronic illnesses other than obesity were compromised in both dimensions. In terms of the number of chronic illnesses reported, the additional presence of obesity was associated with a significant deterioration in physical but not emotional well-being.

Discussion

Overweight and obesity are associated with poor levels of subjective health status, particularly in terms of physical well-being. The limitations in emotional well-being that are reported here and in other studies may be a result of confounding by the presence of accompanying chronic illness.
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Comparison of brain activation during word retrieval done silently and aloud using fMRI.

Issue 2 Vol 42 Published on 2000-03-01 PMID 10744920 PMCID N/A
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DOI: https://doi.org/10.1006/brcg.1999.1100
Authors: H J Rosen In X J G Ojemann In X J M Ollinger In X S E Petersen In X
Abstract: Using functional MRI we compared the patterns of activation in an effortful word retrieval task (stem completion) performed both silently and aloud. The silent and overt conditions showed expected differences in activation magnitude in regions such as primary motor cortex. Some regions, such as frontal operculum and dorsolateral frontal cortex, showed similar activation magnitude across conditions. Thalamus was more active on the left in both conditions and showed a symmetric drop in activity in the silent compared with the overt condition. Putamen was also more active in the overt condition and showed a larger decrease in activity on the right than on the left in the silent compared with the overt condition. Thus it appears that silent and overt performance of this task engage the thalamus and putamen in different ways.
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Insights into cardiac remodelling by multi-modal magnetic resonance imaging and spectroscopy

Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: #
Authors: Steffen E. Petersen In X
Abstract: No Abstract Available
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Diagnostic and prognostic value of ECG-predicted hypertension-mediated left ventricular hypertrophy using machine learning

Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: https://doi.org/10.1101/2024.04.22.24306204
Authors: Hafiz Naderi In X Julia Ramírez In X Stefan van Duijvenboden In X Esmeralda Ruiz Pujadas In X Nay Aung In X Lin Wang In X Bishwas Chamling In X Marcus Dörr In X Marcello Markus In X Anwar Chahal In X Karim Lekadir In X Steffen Petersen In X Patricia Munroe In X
Abstract:

Background

Four hypertension-mediated left ventricular hypertrophy (LVH) phenotypes have been reported using cardiac magnetic resonance (CMR): normal LV, LV remodeling, eccentric and concentric LVH, with varying prognostic implications. The electrocardiogram (ECG) is routinely used to detect LVH, however its capacity to differentiate between LVH phenotypes is unknown. This study aimed to classify hypertension-mediated LVH from the ECG using machine learning (ML) and test for associations of ECG-predicted phenotypes with incident cardiovascular outcomes.

Methods

ECG biomarkers were extracted from the 12-lead ECG of 20,439 hypertensives in UK Biobank (UKB). Classification models integrating ECG and clinical variables were built using logistic regression, support vector machine (SVM) and random forest. The models were trained in 80% of the participants, and the remaining 20% formed the test set. External validation was sought in 877 hypertensives from the Study of Health in Pomerania (SHIP). In the UKB test set, we tested for associations between ECG-predicted LVH phenotypes and incident major adverse cardiovascular events (MACE) and heart failure.

Results

Among UKB participants 19,408 had normal LV, 758 LV remodeling, 181 eccentric and 92 concentric LVH. Classification performance of the three models was comparable, with SVM having a slightly superior performance (accuracy 0.79, sensitivity 0.59, specificity 0.87, AUC 0.69) and similar results observed in SHIP. There was superior prediction of eccentric LVH in both cohorts. In the UKB test set, ECG-predicted eccentric LVH was associated with heart failure (HR 3.42, CI 1.06-9.86).

Conclusions

ECG-based ML classifiers represent a potentially accessible screening strategy for the early detection of hypertension-mediated LVH phenotypes.

Graphical abstract

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Large-scale Mendelian randomization identifies novel pathways as therapeutic targets for heart failure with reduced ejection fraction and with preserved ejection fraction

Open Access Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: https://doi.org/10.1101/2024.03.22.24304728
Authors: Danielle Rasooly In X Claudia Giambartolomei In X Gina Peloso In X Hesam Dashti In X Brian Ferolito In X Daniel Golden In X Andrea Horimoto In X Maik Pietzner In X Eric Farber-Eger In X Quinn Stanton Wells In X Giorgio Bini In X Gabriele Proietti In X Gian Gaetano Tartaglia In X Nicole Kosik In X Peter Wilson In X Lawrence Phillips In X Patricia Munroe In X Steffen Petersen In X Kelly Cho In X John Michael Gaziano In X Andrew Leach In X In X John Whittaker In X Claudia Langenberg In X Nay Aung In X Yan Sun In X Alexandre Pereira In X Jacob Joseph In X Juan Casas In X
Abstract:

ABSTRACT

We used expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) to conduct genome-wide Mendelian randomization (MR) using 27,799 cases of heart failure (HF) with reduced ejection fraction (HFrEF), 27,579 cases of HF with preserved ejection fraction (HFpEF), and 367,267 control individuals from the Million Veteran Program (MVP). We identified 70 HFrEF and 10 HFpEF gene-hits, of which 58 are novel. In 14 known loci for unclassified HF, we identified HFrEF as the subtype responsible for the signal. HFrEF hits ZBTB17 , MTSS1 , PDLIM5 , and MLIP and novel HFpEF hits NFATC2IP, and PABPC4 showed robustness to MR assumptions, support from orthogonal sources, compelling evidence on mechanism of action needed for therapeutic efficacy, and no evidence of an unacceptable safety profile. We strengthen the value of pathways such as ubiquitin-proteasome system, small ubiquitin-related modifier pathway, inflammation, and mitochondrial metabolism as potential therapeutic targets for HF management. We identified IL6R , ADM, and EDNRA as suggestive hits for HFrEF and LPA for HFrEF and HFpEF, which enhances the odds of success for existing cardiovascular investigational drugs targeting. These findings confirm the unique value of human genetic studies in HFrEF and HFpEF for discovery of novel targets and generation of therapeutic target profiles needed to initiate new validation programs in HFrEF and HFpEF preclinical models.
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Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing

Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: https://doi.org/10.1101/2023.12.18.23300178
Authors: James Malcolmson In X Rebecca Hughes In X Tim Husselbury In X Kamran Khan In X Annastazia Learoyd In X Martin Lees In X Eleanor Wicks In X Jamie Smith In X Alexander Simms In X James Moon In X Luis Lopes In X Constantinos O’Mahony In X Neha Sekhri In X Perry Elliott In X Steffen Petersen In X Mehul Dhinoja In X Saidi Mohiddin In X
Abstract:

Background

Patients with refractory symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM) have few therapeutic options. Right ventricular (RV) pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized site-specific-pacing would reduce LVMCO gradients and improve symptoms.

Methods

Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical RV pacing sites were assessed during invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular (AV) delays, defining PPoP, were selected on basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6-months of active PPoP or back-up pacing in a cross-over design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP.

Results

A total of 17 patients were recruited; 16 of whom met primary endpoints. Baseline NYHA was 3±0.6 despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the RV apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and RV apex in 2. The mean baseline gradient of 80±29 mmHg, fell to 31±21 mmHg with best-site pacing, a 60% reduction (p<0.0001). One cardiac vein perforation occurred in one case, and 15 subjects entered cross-over; 2 withdrawals occurred during cross-over. Of the 13 completing cross-over, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 vs 285.8±105.5 meters, p=0.018); other outcome measures also indicated benefit with PPoP.

Conclusions

In a randomized placebo-controlled trial, LV pacing reduces obstruction and improves exercise performance in severely symptomatic LVMCO patients.

Registration

NCT03450252.

Clinical Perspective

What is Known?

Patients with refractory, symptomatic LVMCO present a significant challenge for clinical management, with very few treatment options. Data on the use of right ventricular (RV) pacing in patients with refractory, symptomatic LVMCO indicate suboptimal therapeutic responses whilst pilot data indicate a potential therapeutic role for LV pacing.

What the Study Adds?

Personalized prescription of pacing (PPoP) therapy guided by invasive hemodynamics significantly reduced LVMCO gradients and improved exercise performance in the first randomized, placebo-controlled trial in symptomatic LVMCO. This study provides the basis for a multicenter trial of PPoP for LVMCO and for the use of site-specific pacing in managing other forms of HCM.

Graphical Abstract

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Functional parcellation of the neonatal brain

Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: https://doi.org/10.1101/2023.11.10.566629
Authors: Michael Myers In X Alyssa Labonte In X Evan Gordon In X Timothy Laumann In X Jiaxin Cindy Tu In X Muriah Wheelock In X Ashley Nielsen In X Rebecca Schwarzlose In X Catalina Camacho In X Barbara Warner In X Nandini Raghuraman In X Joan Luby In X Deanna Barch In X Damien Fair In X Steven Petersen In X Cynthia Rogers In X Christopher Smyser In X Chad Sylvester In X
Abstract:

SUMMARY

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

HIGHLIGHTS

Neonatal cortical surface parcels derived based on abrupt changes in functional connectivity (FC) were highly homogenous and were validated in external neonatal datasets. Borders between cortical parcels were smoother (less abrupt) in group-average neonatal data compared to adults, likely due to increased heterogeneity in boundary location across individual neonates. Parcels derived from adults and older infants show poor fit with neonatal resting-state FC data, underscoring the need for a neonatal-specific parcellation.
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Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction

Issue N/A Vol N/A Published on Unknown Date PMID N/A PMCID N/A
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DOI: https://doi.org/10.1101/2023.11.03.23298024
Authors: Celeste McCracken In X Liliana Szabo In X Zaid Abdulelah In X Hajnalka Vago In X Thomas Nichols In X Steffen Petersen In X Stefan Neubauer In X Zahra Raisi-Estabragh In X
Abstract:

Background

The utility of ventricular asymmetry as an imaging biomarker for cardiovascular risk has not been assessed in population cohorts.

Objectives

This study presents a comprehensive assessment of the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases.

Methods

Cardiovascular magnetic resonance (CMR) imaging metrics derived from automated image analysis were examined, along with clinical outcomes ascertained through linked health records. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV, RV) end-diastolic volumes. The normal range for ventricular symmetry was defined in a healthy subset without cardiorespiratory disease. Participants with values outside the 5 th -95 th percentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures.

Results

The analysis includes 44,796 participants (average age 64.1±7.7 years; 51.9% women). Ventricular asymmetry, in either direction, was associated with older age and adverse cardiovascular remodeling. LV-dominance was linked to an array of pre-existing vascular risk factors and cardiovascular diseases, and a two-fold increased risk of incident heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an elevated risk of all-cause mortality.

Conclusions

Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics.

Condensed abstract

Healthy hearts have a predictable symmetry. Asymmetry produced when one, e.g. the left ventricular (LV) volume outweighs the right, or vice versa, could be an important indicator of underlying disorders, and powerful risk indicator for future disease. In this study of 44,796 UK Biobank participants, we show that LV dominance associates significantly with clinical risk factors, existing heart disease, and a two-fold increased risk for future heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an increased risk of all-cause mortality. Ventricular asymmetry is easily calculated from conventional imaging metrics and could be a highly useful addition to the clinician’s toolkit. Central illustration: Ventricular volume asymmetry associates with adverse outcomes
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Healthcare Utilisation of 282,080 Individuals with Long COVID Over Two Years: A Multiple Matched Control Cohort Analysis

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DOI: https://doi.org/10.2139/ssrn.4598962
Authors: Yi Mu In X Ashkan Dashtban In X Mehrdad Mizani In X Christopher Tomlinson In X Mohamed Mohamed In X Mark Ashworth In X Mamas Mamas In X Rouven Priedon In X Steffen Petersen In X Evan Kontopantelis In X Christina Pagel In X Mevhibe Hocaoglu In X Kamlesh Khunti In X Richard Williams In X Johan Hilge Thygesen In X Paula Lorgelly In X Manuel Gomes In X Melissa Heightman In X Amitava Banerjee In X
Abstract: Background: In the UK alone, long Covid(LC) has affected over 2 million individuals, yet health system burden is poorly characterised. Understanding healthcare utilisation will inform clinical, service and policy planning for current and future LC care.

Methods: Using the British Heart Foundation/NHS England Secure Data Environment, we identified individuals ≥18 years of age, diagnosed with LC between January 2020 and January 2023, and age-, sex-, ethnicity-, deprivation-, region-, and comorbidity- matched control groups: (i)COVID only, no LC; (ii)pre-pandemic; (iii)contemporary non-COVID; and (iv)pre-LC(self-controlled, pre-COVID pandemic). Healthcare utilisation (number of consultations/visits per person: primary care (GP), secondary care (outpatient[OP], inpatient[IP] and emergency department[ED], investigations and procedures) and inflation-adjusted cost(£) were estimated for LC and control populations per month, calendar year and pandemic year for each category.

Findings: 282,080 individuals(median[IQR] age 48.0[36.1, 58.9] years; female:62.4%) with LC were included between January 2020 and January 2023. The control groups were COVID only, no LC(n=1,112,370), pre-pandemic(n=1,031,285), contemporary non-COVID(n=1,118,360) and pre-LC(n=282,080). Healthcare utilisation per person (per month/year) was higher in LC than controls across GP and OP. For IP and ED, LC had higher healthcare utilisation than all controls but the COVID only, no LC group(all p<0.0001). Healthcare utilisation of the LC group increased progressively between 2020 and 2023, compared to controls. Cost per patient/year was also higher in individuals with LC(£3,350) than all control groups: pre-pandemic: £1,210(average excess cost: -£2,235 95% CI [-£2,284 -£2,187]), COVID only, no LC: £1,283(-£2,035 [-2,081 -£1,989]) and pre-LC: £870 (-£2,465 [-£2,554 -£2,376]), except for COVID and no LC: £5,961(£2,683 [£2,593 £2,774])(all p<0.0001).

Interpretation: LC has been associated with substantial, persistent healthcare utilisation and cost over the last 3 years. Future funding, resources and staff for LC prevention, treatment and research must be prioritised to reduce sustained primary and secondary healthcare utilisation and costs.

Funding: The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co-development (with NHS England) of the Secure Data Environment service for England, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser’s National Core Studies programme to coordinate national COVID priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians. This work is part of a National Institute for Health Research (NIHR: COV-LT2-0043)-funded LC research programme (STIMULATE-ICP) with epidemiologic and mixed methods studies, including care inequalities and transferability to other LTCs and this complex intervention trial. It was also partially funded by NHS England (7130937).

Declaration of Interest: No competing interest relevant to this publication.

Ethical Approval: The North East - Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD-COVID-UK/COVID-IMPACT research programme (REC No 20/NE/0161) to access, within secure trusted research environments, unconsented, whole-population, de- identified data from electronic health records collected as part of patients’ routine healthcare.
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Global Longitudinal Active Strain Energy Density (GLASED): A Powerful Prognostic Marker in a Community-Based Cohort

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DOI: https://doi.org/10.1101/2023.06.14.23291342
Authors: Nay Aung In X David MacIver In X Henggui Zhang In X Sucharitha Chadalavada In X Steffen Petersen In X
Abstract:

ABSTRACT

BACKGROUND

Identifying the imaging methods that best predict heart failure risk, cardiovascular adverse events and death is crucial for tailoring optimal management. Potential prognostic markers include myocardial mass, left ventricular ejection fraction, myocardial strain, stroke work, contraction fraction, pressure-strain product and a new measurement called global active longitudinal strain density (GLASED).

OBJECTIVES

This study sought to assess the utility of a range of potential prognostic markers of left ventricular structure and contractile function in a community-based cohort.

METHODS

The impact of cardiovascular magnetic resonance image-derived markers, extracted by machine learning algorithms were compared to the future risk of adverse events in a group of 44,957 UK Biobank participants.

RESULTS

Most markers, including the left ventricular ejection fraction, had limited prognostic value. GLASED was significantly associated with heart failure, all-cause mortality and major adverse cardiovascular events with hazard ratios of approximately 1.4.

CONCLUSIONS

GLASED predicted major cardiovascular adverse events and mortality with the highest hazard ratios compared with conventional markers. The routine use of GLASED is recommended for assessing prognosis.

Graphical abstract

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Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity

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DOI: https://doi.org/10.1101/2023.02.25.529948
Authors: Jordan Pierce In X Nathan Petro In X Elizabeth Clancy In X Caterina Gratton In X Steven Petersen In X Maital Neta In X
Abstract: Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggests that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.
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Liver disease is a significant risk factor for cardiovascular outcomes - a UK Biobank study

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DOI: https://doi.org/10.1101/2022.12.08.22283242
Authors: Adriana Roca-Fernandez In X Rajarshi Banerjee In X Helena Thomaides-Brears In X Alison Telford In X Arun Sanyal In X Stefan Neubauer In X Thomas Nichols In X Betty Raman In X Celeste McCracken In X Steffen Petersen In X Ntobeko AB Ntusi In X Daniel Cuthbertson In X Michele Lai In X Andrea Dennis In X Amitava Banerjee In X
Abstract:

ABSTRACT

Background

Chronic liver disease (CLD) and cardiovascular diseases (CVD) share common risk factors; the former is associated with a two-fold greater incidence of CVD. With most CLD being preventable/modifiable, early identification of at high-risk individuals is crucial. Using data from the UK Biobank imaging sub-study, we tested the hypothesis that early signs of liver disease (measured by iron corrected T1-mapping (cT1)) is associated with an increased risk of major cardiovascular events.

Methods

Liver disease activity (cT1) and fat (PDFF) were measured using LiverMultiScan® from images acquired between January-2016 and February-2020 in the UK Biobank imaging sub-study. Multivariable Cox regression was used to explore associations between liver cT1 (MRI) and primary CVD outcomes (coronary artery disease, atrial fibrillation, embolism/vascular events, heart failure and stroke), as well as CVD hospitalisation and all-cause mortality . Other liver blood biomarkers (AST, ALT, AST/ALT ratio, FIB4), general metabolism biomarkers (CRP, HbA1c, systolic blood pressure (SBP), total cholesterol), and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (MetS= at least 3 of these traits: a large waist, high triglycerides, low HDL cholesterol, increased SBP, or elevated HbA1c)

Results

33,616 participants in the UK Biobank imaging sub-study (65 years, mean BMI 26kg/m 2 , mean HbA1c 35mmol/mol) had complete MRI liver data with linked clinical outcomes [median time to major CVD event onset: 1.4 years (range:0.002-5.1); follow-up: 2.5 years (range:1.1-5.2)]. Liver disease activity (cT1), but not liver fat (PDFF), was associated with a higher risk of any major CVD event [HR(CI) 1.14(1.03-1.26), p=0.008], AF [1.30 (1.12-1.5), p<0.001]; HF [1.30 (1.08 - 1.58), p=0.004]; CVD hospitalisation [1.27(1.18-1.387, p<0.001] and all-cause mortality [1.19(1.02-1.38), p=0.026]. FIB4 index, was associated with HF [1.06 (1.01 - 1.10)), p=0.007]. The risk of CVD hospitalisation was also independently associated with cT1 in individuals without MetS [1.26(1.13-1.4), p<0.001].

Conclusion

Liver disease activity, as measured with MRI-derived biomarker cT1, was independently associated with a higher risk of new onset CVD events and all-cause mortality. This association occurred even without pre-existing impairment of metabolic health and was independent of FIB4 or liver fat content. cT1 was identified as a major predictor of adverse CVD outcomes.
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A mind-body interface alternates with effector-specific regions in motor cortex

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DOI: https://doi.org/10.1101/2022.10.26.513940
Authors: Evan Gordon In X Roselyne Chauvin In X Andrew Van In X Aishwarya Rajesh In X Ashley Nielsen In X Dillan Newbold In X Charles Lynch In X Nicole Seider In X Samuel Krimmel In X Kristen Scheidter In X Julia Monk In X Ryland Miller In X Athanasia Metoki In X David Montez In X Annie Zheng In X Immanuel Elbau In X Thomas Madison In X Tomoyuki Nishino In X Michael Myers In X Sydney Kaplan In X Carolina Badke D’Andrea In X Damion Demeter In X Matthew Feigelis In X Deanna Barch In X Christopher Smyser In X Cynthia Rogers In X Jan Zimmermann In X Kelly Botteron In X John Pruett In X Jon Willie In X Peter Brunner In X Joshua Shimony In X Benjamin Kay In X Scott Marek In X Scott Norris In X Caterina Gratton In X Chad Sylvester In X Jonathan Power In X Conor Liston In X Deanna Greene In X Jarod Roland In X Steven Petersen In X Marcus Raichle In X Timothy Laumann In X Damien Fair In X Nico U.F. Dosenbach In X
Abstract:

SUMMARY

Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down precentral gyrus from foot to face representations 1,2 . The motor homunculus has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric functional zones 3 and maps of complex actions 4 . Using our highest precision functional magnetic resonance imaging (fMRI) data and methods, we discovered that the classic homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function, alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, and to prefrontal, insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive action 5 and physiological control 6 , arousal 7 , and processing of errors 8 and pain 9 . This interdigitation of action control-linked and motor effector regions was independently verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI revealed potential cross-species analogues and developmental precursors of the inter-effector system. An extensive battery of motor and action fMRI tasks documented concentric somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-effector regions lacked movement specificity and co-activated during action planning (coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These results, together with prior work demonstrating stimulation-evoked complex actions 4 and connectivity to internal organs (e.g., adrenal medulla) 10 , suggest that M1 is punctuated by an integrative system for implementing whole-body action plans. Thus, two parallel systems intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot, hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative whole-organism coordination of goals, physiology, and body movement.
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The cingulo-opercular network is composed of two distinct sub-systems

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DOI: https://doi.org/10.1101/2022.09.16.508254
Authors: Caterina Gratton In X Ally Dworetsky In X Babatunde Adeyemo In X Benjamin Seitzman In X Derek Smith In X Steven Petersen In X Maital Neta In X
Abstract:

ABSTRACT

The cingulo-opercular (CO) network and its two best studied regions – the dorsal anterior cingulate and anterior insula – have been linked to task control, but also implicated in many additional processes across cognitive, social, and emotional domains. However, most prior work investigating the CO network has used a group-average approach, which may mix signals across nearby regions that vary across individuals. Here, we reevaluate the CO network’s role in task control with both task and rest fMRI, using regions with a high probability of CO network agreement across individuals. Hierarchical clustering analyses suggest heterogeneity in the CO network’s task response properties, with one sub-system (CO1) showing consistency with prior task control characterizations while another sub-system (CO2) has weak task control responses, but preserved ties to pain and motor functions. Resting-state connectivity confirms subtle differences in the architecture of these two sub-systems. This evidence suggests that, when individual variation in network locations is addressed, the CO network includes (at least) two linked sub-systems with differential roles in task control and other cognitive/motor/interoceptive responses, which may help explain varied accounts of its functions. We propose that this fractionation may reflect expansion of primary CO body-oriented control functions to broader domain-general contexts.
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A Structural Heart-Brain Axis Mediates the Association Between Cardiovascular Risk and Cognitive Function

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DOI: https://doi.org/10.1101/2022.09.15.22279275
Authors: Akshay Jaggi In X Eleanor L.S. Conole In X Zahra Raisi-Estabragh In X Polyxeni Gkontra In X Celeste McCracken In X Stefan Neubauer In X Steffen Petersen In X Simon Cox In X Karim Lekadir In X
Abstract: Elevated vascular disease risk associates with poorer cognitive function, but the mechanism for this link is poorly understood. A leading theory, the structural-functional model argues that vascular risk may drive adverse cardiac remodelling, which in turn leads to chronic cerebral hypoperfusion and subsequent brain structural damage. This model predicts that variation in heart and brain structure should associate with both greater vascular risk and lower cognitive function. This study tests that prediction in a large sample of the UK Biobank (N=11,962). We assemble and summarise vascular risk factors, cardiac magnetic resonance radiomics, brain structural and diffusion MRI indices, and cognitive assessment. We also extract ‘heart-brain axes’ capturing the covariation in heart and brain structure. Many heart and brain measures partially explain the vascular risk – cognitive function association, like left ventricular end-diastolic volume and grey matter volume. Notably, a heart-brain axis, capturing correlation between lower myocardial intensity, lower grey matter volume, and poorer thalamic white matter integrity, completely mediates the association, supporting the structural-functional model. Our findings also complicate this theory by finding that brain structural variation cannot completely explain the heart structure – cognitive function association. Our results broadly offer evidence for the structural functional hypothesis, identify imaging biomarkers for this association by considering covariation in heart and brain structure, and generate novel hypotheses about how cardiovascular risk may link to cognitive function.
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Screening for Pathogenic Variants in Cardiomyopathy Genes Predicts Mortality and Composite Outcomes in UK Biobank

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DOI: https://doi.org/10.1101/2022.06.27.22276949
Authors: Babken Asatryan In X Ravi Shah In X Ghaith Sharaf Dabbagh In X Andrew Landstrom In X Dawood Darbar In X Mohammed Khanji In X Luis Lopes In X Stefan van Duijvenboden In X Daniele Muser In X Aaron Mark Lee In X Christopher Haggerty In X Pankaj Arora In X Christopher Semsarian In X Tobias Reichlin In X Virend Somers In X Anjali Owens In X Steffen Petersen In X Rajat Deo In X Patricia Munroe In X Nay Aung In X Anwar Chahal In X
Abstract:

Background

Inherited cardiomyopathies can present with broad variation of phenotype. Data are limited regarding genetic screening strategies and outcomes associated with putative pathogenic variants (PuPV) in cardiomyopathy-associated genes in the general population.

Objective

We aimed to determine the risk of mortality and cardiomyopathy-related outcomes associated with PuPV in cardiomyopathy-associated genes in UK Biobank.

Methods

Using whole exome sequencing data, variants in dilated, hypertrophic and arrhythmogenic cardiomyopathy-associated genes with at least limited evidence of disease causality according to ClinGen Expert Panel curations, were annotated using REVEL (≥0.65) and ANNOVAR (predicted loss of function) to identify PuPVs. Individuals with PuPV comprised the genotype-positive (G+) and those without PuPV the genotype-negative (G-) cohorts. Group comparisons were made using time-to-event analyses for the primary (all-cause mortality) and secondary outcomes (diagnosis of cardiomyopathy; composite outcome of diagnosis of cardiomyopathy, heart failure, arrhythmia, stroke, and death).

Results

Among 200,619 participants, 22,401 (11.2%) were found to host ≥1 PuPV in cardiomyopathy-associated genes (G+). After adjusting for age and sex, G+ individuals had increased all-cause mortality [HR 1.07 (95%CI 1.02-1.13; p=0.011)] and increased rates of diagnosis of cardiomyopathy later in life [HR 2.37 (95%CI 1.98-2.85; p<0.0001)], which further increased in those with PuPV in definitive/strong evidence ClinGen genes [3.25 (95%CI 2.63-4.00; p<0.0001)]. G+ individuals had a higher risk of developing the composite outcome [HR 1.11 (95%CI 1.06-1.15; p<0.0001)].

Conclusions

Adults with PuPV in cardiomyopathy-associated genes have higher all-cause mortality and increased risk of developing cardiomyopathy-associated features and complications, compared to genotype-negative controls.

Condensed Abstract

Leveraging the UK Biobank prospective cohort, we analyzed whole exome sequencing data in dilated, hypertrophic and arrhythmogenic cardiomyopathy-associated genes using a population screening ‘genotype-first’ approach. Individuals with putative pathogenic variants in genes implicated in cardiomyopathies showed an increased risk of all-cause mortality, higher risk of developing clinical cardiomyopathy later in life, and higher risk of a composite outcome (cardiomyopathy, heart failure, arrhythmia, stroke, and death) compared to genotype-negative controls. These findings highlight the potential role of ‘genotype-first’ approach in elevating personalized medicine into population level precision health in the future.
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Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure

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DOI: https://doi.org/10.1101/2022.04.14.22273877
Authors: Danielle Rasooly In X Gina Peloso In X Alexandre Pereira In X Hesam Dashti In X Claudia Giambartolomei In X Eleanor Wheeler In X Nay Aung In X Brian Ferolito In X Maik Pietzner In X Eric Farber-Eger In X Quinn Stanton Wells In X Nicole Kosik In X Liam Gaziano In X Daniel Posner In X Patrícia Bento In X Qin Hui In X Chang Liu In X Krishna Aragam In X Zeyuan Wang In X Brian Charest In X Jennifer Huffman In X Peter W.F. Wilson In X Lawrence Phillips In X John Whittaker In X Patricia Munroe In X Steffen Petersen In X Steffen Petersen In X Kelly Cho In X Andrew Leach In X María Paula Magariños In X John Michael Gaziano In X In X Claudia Langenberg In X Yan Sun In X Jacob Joseph In X Juan Casas In X
Abstract: We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven ( CAMK2D , PRKD1 , PRKD3 , MAPK3 , TNFSF12 , APOC3 and NAE1 ) proteins as potential targets for interventions to be used in primary prevention of heart failure.
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Minimising Multi-Centre Radiomics Variability Through Image Normalisation: A Pilot Study

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DOI: https://doi.org/10.21203/rs.3.rs-1250808/v1
Authors: Víctor Campello In X Carlos Martín-Isla In X Cristian Izquierdo In X Andrea Guala In X José Rodríguez-Palomares In X David Viladés In X Martín Descalzo In X Mahir Karakas In X Ersin Çavus In X Zahra Raisi-Estabragh In X Steffen Petersen In X Sergio Escalera In X Santi Seguí In X Karim Lekadir In X
Abstract: Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image-and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n=112) and hypertrophic cardiomyopathy (n=106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features’ variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: 1) the amount of centre-related information encoded in normalised features (centre identification) and 2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification (0.75 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall (0.47 ± 0.13). In conclusion, centre-related information removal did not imply good generalisation ability for classification.
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BOLD cofluctuation ‘events’ are predicted from static functional connectivity

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DOI: https://doi.org/10.1101/2022.01.24.477543
Authors: Zach Ladwig In X Benjamin Seitzman In X Ally Dworetsky In X Yuhua Yu In X Babatunde Adeyemo In X Derek Smith In X Steven Petersen In X Caterina Gratton In X
Abstract:

ABSTRACT

Recent work identified single time points (“events”) of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or if it could arise from sampling variability alone. First, we show that events are not discrete – there is a gradually increasing relationship between network structure and cofluctuation; ∼50% of samples show very strong network structure. Second, using simulations we show that this relationship is predicted from sampling variability on static FC. Finally, we show that randomly selected points can capture network structure about as well as events, largely because of their temporal spacing. Together, these results suggest that, while events exhibit particularly strong representations of static FC, there is little evidence that events are unique timepoints that drive FC structure. Instead, a parsimonious explanation for the data is that events arise from a single static, but noisy, FC structure.

HIGHLIGHTS

Past results suggested high cofluctuation BOLD “events” drive fMRI functional connectivity, FC Here, events were examined in both real fMRI data and a stationary null model to test this model In real data, >50% of BOLD timepoints show high modularity and similarity to time- averaged FC Stationary null models identified events with similar behavior to real data Events may not be a transient driver of static FC, but rather an expected outcome of it.
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An agenda-setting paper on data sharing platforms: euCanSHare workshop

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DOI: https://doi.org/10.12688/openreseurope.13860.2
Authors: Thijs Devriendt In X Clemens Ammann In X Folkert W. Asselbergs In X Alexander Bernier In X Rodrigo Costas In X Matthias Friedrich In X Josep Gelpi In X Marjo-Riitta Jarvelin In X Kari Kuulasmaa In X Karim Lekadir In X Michaela Th. Mayrhofer In X Vaclav Papez In X Gerard Pasterkamp In X Steffen Petersen In X Carsten Oliver Schmidt In X Jeanette Schulz-Menger In X Stefan Söderberg In X Mahsa Shabani In X Giovanni Veronesi In X Darian Steven Viezzer In X Pascal Borry In X
Abstract: Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.
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The Frequency, Penetrance and Variable Expressivity of Dilated Cardiomyopathy-Associated Putative Pathogenic Gene Variants in UK Biobank Participants

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DOI: https://doi.org/10.1101/2021.11.22.21266651
Authors: Ravi Shah In X Babken Asatryan In X Ghaith Sharaf Dabbagh In X Nay Aung In X Mohammed Khanji In X Luis Lopes In X Stefan van Duijvenboden In X Anthony Holmes In X Daniele Muser In X Andrew Landstrom In X Aaron Mark Lee In X Pankaj Arora In X Christopher Semsarian In X Virend Somers In X Anjali Owens In X Patricia Munroe In X Steffen Petersen In X Anwar Chahal In X
Abstract:

ABSTRACT

Background

There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general, adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional and arrhythmic disease features.

Methods

UK Biobank participants who had undergone whole exome sequencing (WES), ECG and cardiovascular magnetic resonance (CMR) imaging were selected for study. Three different variant calling strategies (one primary and two secondary) were used to identify subjects with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded to either 1) DCM (clinical or CMR diagnosis); 2) early DCM features, including arrhythmia and/or conduction disease, isolated ventricular dilation, and hypokinetic non-dilated cardiomyopathy; or 3) phenotype-negative.

Results

Among 18,665 individuals included in the study, 1,463 (7.8%) subjects possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and CMR analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in 15.9% of individuals with putative pathogenic variants. Arrhythmias and/or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic non-dilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all three variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes, as compared to those with variants in moderate/limited evidence genes.

Conclusions

In the UK Biobank, approximately 1/6 of adults with putative pathogenic variants in DCM genes exhibited a subclinical phenotype based on ECG and/or CMR, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation/dysfunction.

Clinical Perspective

What is new?

Among individuals with putative pathogenic DCM gene variants, subclinical DCM and early DCM features, detected by ECG and/or CMR, were nearly four times more common than clinically manifest DCM or early features (23.7% vs. 6.1%). Over 90% of subjects with a putative pathogenic variant in DCM-associated genes did not have a prior history of DCM. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes (13.9% for clinical and subclinical), as compared to those with variants in moderate/limited evidence genes, but there was no significant difference in combined clinical/subclinical phenotype by cluster. The overall clinical/subclinical penetrance of DCM-associated single putative pathogenic variants was highly variable between genes, ranging from 0 to 66.7%.

What are the clinical implications?

Arrhythmias and cardiac conduction disease are the most common early manifestation of putative pathogenic variants implicated in DCM, mostly occurring prior to the development of structural/functional abnormalities. A genotype-first screening approach for DCM using a large genetic panel is currently not suitable in the general population due to incomplete understanding of DCM genetic architecture and reduced penetrance of DCM-associated putative pathogenic variants.

Journal Subject Terms

Cardiomyopathy; Genetics; Sudden Cardiac Death
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Longitudinal Changes of Cardiac and Aortic Imaging Phenotypes Following COVID-19 in the UK Biobank Cohort

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DOI: https://doi.org/10.1101/2021.11.04.21265918
Authors: Wenjia Bai In X Betty Raman In X Steffen Petersen In X Stefan Neubauer In X Zahra Raisi-Estabragh In X Nay Aung In X Nicholas Harvey In X Naomi Allen In X Rory Collins In X Paul Matthews In X
Abstract: Case studies conducted after recovery from acute infection with SARS-CoV-2 have frequently identified abnormalities on CMR imaging, suggesting the possibility that SARS-CoV-2 infection commonly leads to cardiac pathology. However, these observations have not been able to distinguish between associations that reflect pre-existing cardiac abnormalities (that might confer a greater likelihood of more severe infection) from those that arise as consequences of infection. To address this question, UK Biobank volunteers (n=1285; 54.5% women; mean age at baseline, 59.8 years old; 96.3% white) who attended an imaging assessment including cardiac magnetic resonance (CMR) before the start of the COVID-19 pandemic were invited to attend a second imaging assessment in 2021. Cases with evidence of previous SARS-CoV-2 infection were identified through linkage to PCR-testing or other medical records, or a positive antibody lateral flow test; n=640 in data available on 22 Sep 2021) and were matched to controls with no evidence of previous infection (n=645). The majority of these infections were milder and did not involve hospitalisation. Measures of cardiac and aortic structure and function were derived from the CMR images obtained on the cases before and after SARS-CoV-2 infection from images for the controls obtained over the same time interval using a previously validated, automated algorithm. Cases and controls had similar cardiac and aortic imaging phenotypes at their first imaging assessment. Changes between CMR imaging measures in cases before and after infection were not significantly different from those in the matched control group. Additional adjustment for comorbidities made no material difference to the results. While these results are preliminary and limited to imaging metrics derived from automated analyses, they do not suggest clinically significant persistent cardiac pathology in the UK Biobank population after generally milder (non-hospitalised) SARS-CoV-2 infection.
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Two common and distinct forms of variation in human functional brain networks

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DOI: https://doi.org/10.1101/2021.09.17.460799
Authors: Ally Dworetsky In X Benjamin Seitzman In X Babatunde Adeyemo In X Ashley Nielsen In X Alexander Hatoum In X Derek Smith In X Thomas Nichols In X Maital Neta In X Steven Petersen In X Caterina Gratton In X
Abstract: The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most prior work treats all individual differences as equivalent and primarily linked to boundary shifts between the borders of regions, here we show that cortical ‘variants’ actually occur in two different forms. In addition to border shifts, variants also occur at a distance from their typical position, forming ectopic intrusions. Both forms of variants are common across individuals, but the forms differ in their location, network associations, and activations during tasks, patterns that replicate across datasets and methods of definition. Border shift variants also track significantly more with shared genetics than ectopic variants, suggesting a closer link between ectopic variants and environmental influences. Further, variant properties are categorically different between subgroups of individuals. Exploratory evidence suggests that variants can predict individual differences in behavior, but the two forms differ in which behavioral phenotypes they predict. This work argues that individual differences in brain organization commonly occur in two dissociable forms – border shifts and ectopic intrusions – suggesting that these types of variation are indexing distinct forms of cortical variation that must be separately accounted for in the analysis of cortical systems across people. This work expands our knowledge of cortical variation in humans and helps reconceptualize the discussion of how cortical systems variability arises and links to individual differences in cognition and behavior.
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Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-based Segmentation

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DOI: https://doi.org/10.1101/2021.07.19.21260749
Authors: Esther Puyol-Antón In X Bram Ruijsink In X Jorge Mariscal Harana In X Stefan Piechnik In X Stefan Neubauer In X Steffen Petersen In X Reza Razavi In X Phil Chowienczyk In X Andrew King In X
Abstract:

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias.

Objectives

To perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5±7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

We found statistically significant differences in Dice scores (white ∼94% vs minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders.

Conclusions

We have shown that racial bias can exist in DL-based cine CMR segmentation models. We believe that this bias is due to the imbalanced nature of the training data (combined with physiological differences). This is supported by the results which show racial bias but not sex bias when trained using the UK Biobank database, which is sex-balanced but not race-balanced.

Condensed Abstract

AI algorithms have the potential to reflect or exacerbate racial/sex disparities in healthcare. We aimed to determine the impact of sex and race on the performance of an AI segmentation model for automatic CMR quantification in a cohort of 5,903 subjects from the UK Biobank database, which is sex-balanced but not race-balanced. We tested the model’s bias in performance using Dice scores and absolute/relative errors in measurements of biventricular volumes and function. Our study demonstrates that the model had a racial bias but no sex bias, and that subject characteristics and co-morbidities could not explain this bias.
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Improving Robustness of Automatic Cardiac Function Quantification From Cine Magnetic Resonance Imaging Using Synthetic Image Data

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DOI: https://doi.org/10.21203/rs.3.rs-715226/v1
Authors: Bogdan Gheorghiță In X Lucian Itu In X Puneet Sharma In X Constantin Suciu In X Jens Wetzl In X Christian Geppert In X Mohamed Ali Asik Ali In X Aaron Lee In X Stefan Piechnik In X Stefan Neubauer In X Steffen Petersen In X Jeanette Schulz-Menger In X Teodora Chitiboi In X
Abstract: Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.
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Brain Age Estimation at Tract Group Level and its Association with Daily Life Measures, Cardiac Risk Factors and Genetic Variants

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DOI: https://doi.org/10.21203/rs.3.rs-518759/v1
Authors: Ahmed Salih In X Ilaria Boscolo Galazzo In X Zahra Raisi-Estabragh In X Elisa Rauseo In X Polyxeni Gkontra In X Steffen Petersen In X Karim Lekadir In X André Altmann In X Petia Radeva In X Gloria Menegaz In X
Abstract: Brain age can be estimated using different MRI modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15335 healthy participants from United Kingdom Biobank relying on diffusion MRI image derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an ensemble model that gathers all the considered white matter bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. Our study revealed that the limbic tracts experience less brain aging compared to other tract groups, Brainstem tracts ages relatively faster while the other tract groups present similar brain aging patterns. The model achieved 5.86 mean absolute error (MAE) for brainstem, 5.08 for limbic tracts and around 5.2 for the other three tract groups while, the ensemble model 4.55. Moreover, the results suggest that limbic tracts are more affected by daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p-value < 5E-8) associated with brain age delta in projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes.
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Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks

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DOI: https://doi.org/10.1101/2021.04.12.439415
Authors: Evan Gordon In X Timothy Laumann In X Scott Marek In X Dillan Newbold In X Jacqueline Hampton In X Nicole Seider In X David Montez In X Ashley Nielsen In X Andrew Van In X Annie Zheng In X Ryland Miller In X Joshua Siegel In X Benjamin Kay In X Abraham Snyder In X Deanna Greene In X Bradley Schlaggar In X Steven Petersen In X Steven Nelson In X Nico U.F. Dosenbach In X
Abstract: The striatum is interconnected with the cerebral cortex via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate cortico-striatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited by the practice of averaging neuroimaging data across individuals. Here we utilized highly-sampled resting-state functional connectivity MRI for individually-specific precision functional mapping of cortico-striatal connections. We identified ten discrete, individual-specific subnetworks linking cortex—predominately frontal cortex—to striatum. These subnetworks included previously unknown striatal connections to the human language network. The discrete subnetworks formed a stepped rostral-caudal gradient progressing from nucleus accumbens to posterior putamen; this organization was strongest for projections from medial frontal cortex. The stepped gradient organization fit patterns of fronto-striatal connections better than a smooth, continuous gradient. Thus, precision subnetworks identify detailed, individual-specific stepped gradients of cortico-striatal connectivity that include human-specific language networks.
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Older biological age is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

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DOI: https://doi.org/10.1101/2021.03.20.21254010
Authors: Qingning Wang In X Veryan Codd In X Zahra Raisi-Estabragh In X Crispin Musicha In X Vasiliki Bountziouka In X Stephen Kaptoge In X Elias Allara In X Emanuele Di Angelantonio In X Adam Butterworth In X Angela Wood In X John Thompson In X Steffen Petersen In X Nicholas Harvey In X John Danesh In X Nilesh Samani In X Christopher Nelson In X
Abstract:

Background

Older chronological age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain, however, whether older biological age, as assessed by leucocyte telomere length (LTL), is also associated with COVID-19 outcomes.

Methods

We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 131 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships.

Findings

Of 6,775 participants in UKB who had tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·31; P=0·004) per 1-SD shorter usual LTL, after adjustment for chronological age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant.

Interpretation

Shorter LTL, indicative of older biological age, is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including chronological age. Further data are needed to determine whether this association reflects causality.

Funding

UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.
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Precision Diffusion Imaging

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DOI: https://doi.org/10.1101/2021.02.19.432023
Authors: Nicole Seider In X Babatunde Adeyemo In X Ryland Miller In X Dillan Newbold In X Jacqueline Hampton In X Kristen Scheidter In X Jerrel Rutlin In X Timothy Laumann In X Jarod Roland In X David Montez In X Andrew Van In X Annie Zheng In X Scott Marek In X Benjamin Kay In X Larry Bretthorst In X Bradley Schlaggar In X Deanna Greene In X Yong Wang In X Steven Petersen In X Evan Gordon In X Abraham Snyder In X Joshua Shimony In X Nico Dosenbach In X
Abstract: Diffusion tensor imaging (DTI) aims to non-invasively characterize the anatomy and integrity of the brain’s white matter fibers. To establish individual-specific precision approaches for DTI, we defined its reliability and accuracy as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). DTI methods that allow for crossing fibers (BedpostX [BPX], Q-Ball Imaging [QBI]) estimated excess fibers when insufficient data was present and when the data did not match the model priors. To reduce such overfitting, we developed a novel crossing-fiber diffusion imaging method, Bayesian Multi-tensor Model-selection (BaMM), that is designed for high-quality repeated sampling data sets. BaMM was robust to overfitting, showing high reliability and the relatively best crossing-fiber accuracy with increasing amounts of diffusion data. Thus, the choice of diffusion imaging analysis method is important for the success of individual-specific diffusion imaging. Importantly, for potential clinical applications of individual-specific precision DTI, such as deep brain stimulation (DBS), other forms of neuromodulation or neurosurgical planning, the data quantities required to achieve DTI reliability are lower than for functional MRI measures.
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Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19

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DOI: https://doi.org/10.12688/wellcomeopenres.16051.2
Authors: João Augusto In X Katia Menacho In X Mervyn Andiapen In X Ruth Bowles In X Maudrian Burton In X Sophie Welch In X Anish Bhuva In X Andreas Seraphim In X Corinna Pade In X George Joy In X Melanie Jensen In X Rhodri Davies In X Gabriella Captur In X Marianna Fontana In X Hugh Montgomery In X Ben O’Brien In X Aroon Hingorani In X Teresa Cutino-Moguel In X Áine McKnight In X Hakam Abbass In X Mashael Alfarih In X Zoe Alldis In X Georgina Baca In X Alex Boulter In X Olivia Bracken In X Natalie Bullock In X Nicola Champion In X Carmen Chan In X Xose Couto-Parada In X Keenan Dieobi-Anene In X Karen Feehan In X Gemma Figtree In X Melanie Figtree In X Malcolm Finlay In X Nasim Forooghi In X Joseph Gibbons In X Peter Griffiths In X Matt Hamblin In X Lee Howes In X Ivie Itua In X Meleri Jones In X Victor Jardim In X Vikas Kapil In X Wing-Yiu Jason Lee In X Vineela Mandadapu In X Celina Mfuko In X Oliver Mitchelmore In X Susana Palma In X Kush Patel In X Steffen Petersen In X Brian Piniera In X Rosalind Raine In X Alicja Rapala In X Amy Richards In X Genine Sambile In X Jorge Couto de Sousa In X Michelle Sugimoto In X George Thornton In X Jessica Artico In X Dan Zahedi In X Ruth Parker In X Mathew Robathan In X Lauren Hickling In X Ntobeko Ntusi In X Amanda Semper In X Tim Brooks In X Jessica Jones In X Art Tucker In X Jessry Veerapen In X Mohit Vijayakumar In X Theresa Wodehouse In X Lucinda Wynne In X Thomas Treibel In X Mahdad Noursadeghi In X Charlotte Manisty In X James Moon In X
Abstract:

Background:

Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory.

Methods:

We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months.

Results:

Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies.

Conclusions:

This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/ .
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Probabilistic mapping of human functional brain networks identifies regions of high group consensus

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DOI: https://doi.org/10.1101/2020.09.28.313791
Authors: Ally Dworetsky In X Benjamin Seitzman In X Babatunde Adeyemo In X Maital Neta In X Rebecca Coalson In X Steven Petersen In X Caterina Gratton In X
Abstract: Many recent developments surrounding the functional network organization of the human brain have focused on data that have been averaged across groups of individuals. While such group-level approaches have shed considerable light on the brain’s large-scale distributed systems, they conceal individual differences in network organization, which recent work has demonstrated to be common and widespread. This individual variability produces noise in group analyses, which may average together regions that are part of different functional systems across participants, limiting interpretability. However, cost and feasibility constraints may limit the possibility for individual-level mapping within studies. Here our goal was to leverage information about individual-level brain organization to probabilistically map common functional systems and identify locations of high inter-subject consensus for use in future group analyses. We probabilistically mapped 14 functional networks in multiple datasets with relatively high amounts of data. All networks show “core” (high-probability) regions, but differ from one another in the extent of their higher-variability components. These patterns replicate well across four datasets with different participants and scanning parameters. We produced a set of high-probability regions of interest (ROIs) from these probabilistic maps; these and the probabilistic maps are made publicly available, together with a tool for querying the network membership probabilities associated with any given cortical location. These quantitative estimates and public tools may allow researchers to apply information about inter-subject consensus to their own fMRI studies, improving inferences about systems and their functional specializations.
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Cingulo-Opercular Control Network Supports Disused Motor Circuits in Standby Mode

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DOI: https://doi.org/10.1101/2020.09.03.275479
Authors: Dillan Newbold In X Evan Gordon In X Timothy Laumann In X Nicole Seider In X David Montez In X Sarah Gross In X Annie Zheng In X Ashley Nielsen In X Catherine Hoyt In X Jacqueline Hampton In X Mario Ortega In X Babatunde Adeyemo In X Derek Miller In X Andrew Van In X Scott Marek In X Bradley Schlaggar In X Alexandre Carter In X Benjamin Kay In X Deanna Greene In X Marcus Raichle In X Steven Petersen In X Abraham Snyder In X Nico U.F. Dosenbach In X
Abstract: Whole-brain resting-state functional MRI (rs-fMRI) during two weeks of limb constraint revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula (1). Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

Significance

Many studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive control regions in the cingulo-opercular network (CON). Two complementary analyses, pulse censoring and pulse addition, demonstrated that increased functional connectivity between the CON and disused motor regions was driven by large, spontaneous pulses of activity in the CON and disused motor regions. These results point to a previously unknown role for the CON in supporting motor plasticity and reveal spontaneous activity pulses as a novel mechanism for reorganizing the brain’s functional connections.
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Towards Reproducible Brain-Wide Association Studies

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DOI: https://doi.org/10.1101/2020.08.21.257758
Authors: Scott Marek In X Brenden Tervo-Clemmens In X Finnegan Calabro In X David Montez In X Benjamin Kay In X Alexander Hatoum In X Meghan Rose Donohue In X William Foran In X Ryland Miller In X Eric Feczko In X Oscar Miranda-Dominguez In X Alice Graham In X Eric Earl In X Anders Perrone In X Michaela Cordova In X Olivia Doyle In X Lucille Moore In X Greg Conan In X Johnny Uriarte In X Kathy Snider In X Angela Tam In X Jianzhong Chen In X Dillan Newbold In X Annie Zheng In X Nicole Seider In X Andrew Van In X Timothy Laumann In X Wesley Thompson In X Deanna Greene In X Steven Petersen In X Thomas Nichols In X B.T. Thomas Yeo In X Deanna Barch In X Hugh Garavan In X Beatriz Luna In X Damien Fair In X Nico U.F. Dosenbach In X
Abstract: Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25) 1,2 . Leveraging the Adolescent Brain Cognitive Development (ABCD) Study 3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures 4–6 ; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N⪆2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.
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Network variants are similar between task and rest states

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DOI: https://doi.org/10.1101/2020.07.30.229492
Authors: Brian Kraus In X Diana Perez In X Zach Ladwig In X Benjamin Seitzman In X Ally Dworetsky In X Steven Petersen In X Caterina Gratton In X
Abstract: Recent work has demonstrated that individual-specific variations in functional networks (that we call “network variants”) can be identified in individuals using functional magnetic resonance imaging (fMRI). These network variants exhibit reliability over time with resting-state fMRI data. These properties have suggested that network variants may be trait-like markers of individual differences in brain organization. Another test of this conclusion would be to examine if network variants are stable between task and rest states. Here, we use precision data from the Midnight Scan Club (MSC) to demonstrate that (1) task data can be used to identify network variants reliably, (2) these network variants show substantial spatial overlap with those observed in rest, although state-specific effects are present, (3) network variants assign to similar canonical functional networks in different states, and (4) single tasks or a combination of multiple tasks produce similar network variants to rest. Together, these findings further reinforce the trait-like nature of network variants and demonstrate the utility of using task data to define network variants.
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Greater risk of severe COVID-19 in non-White ethnicities is not explained by cardiometabolic, socioeconomic, or behavioural factors, or by 25(OH)-vitamin D status: study of 1,326 cases from the UK Biobank

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DOI: https://doi.org/10.1101/2020.06.01.20118943
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Mae Bethell In X Jackie Cooper In X Cyrus Cooper In X Mark Caulfield In X Patricia Munroe In X Nicholas Harvey In X Steffen Petersen In X
Abstract:

Background

We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and non-White ethnicities is explained by cardiometabolic, socio-economic, or behavioural factors.

Methods

We studied 4,510 UK Biobank participants tested for COVID-19 (positive, n = 1,326). Multivariate logistic regression models including age, sex, and ethnicity were used to test whether addition of: 1)cardiometabolic factors (diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking, BMI); 2)25(OH)-vitamin D; 3)poor diet; 4)Townsend deprivation score; 5)housing (home type, overcrowding); or 6)behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status.

Results

There was over-representation of men and non-White ethnicities in the COVID-19 positive group. Non-Whites had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and flats/apartments. Male sex, non-White ethnicity, higher BMI, Townsend deprivation score, and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations.

Conclusions

Sex and ethnicity differential pattern of COVID-19 is not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels, or socio-economic factors. Investigation of alternative biological pathways and different genetic susceptibilities is warranted.
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NON-WHITE ETHNICITY, MALE SEX, AND HIGHER BODY MASS INDEX, BUT NOT MEDICATIONS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ARE ASSOCIATED WITH CORONAVIRUS DISEASE 2019 (COVID-19) HOSPITALISATION: REVIEW OF THE FIRST 669 CASES FROM THE UK BIOBANK

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DOI: https://doi.org/10.1101/2020.05.10.20096925
Authors: Zahra Raisi-Estabragh In X Celeste McCracken In X Maddalena Ardissino In X Mae Bethell In X Jackie Cooper In X Cyrus Cooper In X Nicholas Harvey In X Steffen Petersen In X
Abstract:

Background:

Cardiometabolic morbidity and medications, specifically Angiotensin Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs), have been linked with adverse outcomes from coronavirus disease 2019 (COVID-19). This study aims to investigate factors associated with COVID-19 positivity for the first 669 UK Biobank participants; compared with individuals who tested negative, and with the untested, presumed negative, rest of the population.

Methods:

We studied 1,474 participants from the UK Biobank who had been tested for COVID-19. Given UK testing policy, this implies a hospital setting, suggesting at least moderate to severe symptoms. We considered the following exposures: age, sex, ethnicity, body mass index (BMI), diabetes, hypertension, hypercholesterolaemia, ACEi/ARB use, prior myocardial infarction (MI), and smoking. We undertook comparisons between: 1) COVID-19 positive and COVID-19 tested negative participants; and 2) COVID-19 tested positive and the remaining participants (tested negative plus untested, n=501,837). Logistic regression models were used to investigate univariate and mutually adjusted associations.

Results:

Among participants tested for COVID-19, non-white ethnicity, male sex, and greater BMI were independently associated with COVID-19 positive result. Non-white ethnicity, male sex, greater BMI, diabetes, hypertension, prior MI, and smoking were independently associated with COVID-19 positivity compared to the remining cohort (test negatives plus untested). However, similar associations were observed when comparing those who tested negative for COVID-19 with the untested cohort; suggesting that these factors associate with general hospitalisation rather than specifically with COVID-19.

Conclusions:

Among participants tested for COVID-19 with presumed moderate to severe symptoms in a hospital setting, non-white ethnicity, male sex, and higher BMI are associated with a positive result. Other cardiometabolic morbidities confer increased risk of hospitalisation, without specificity for COVID-19. Notably, ACE/ARB use did not associate with COVID-19 status.
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Age-dependent differences in functional brain networks are atypical in Tourette syndrome

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DOI: https://doi.org/10.1101/2020.04.06.20049817
Authors: Ashley Nielsen In X Caterina Gratton In X Soyoung Kim In X Jessica Church In X Kevin Black In X Steven Petersen In X Bradley Schlaggar In X Deanna Greene In X
Abstract: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. TS is complex, with symptoms that involve sensory, motor, and top-down control processes and that fluctuate over the course of development. While many have studied atypical brain structure and function associated with TS, the neural substrates supporting the complex range and time-course of symptoms is largely understudied. Here, we used functional connectivity MRI to examine functional networks across the whole-brain in children and adults with TS. To investigate the functional neuroanatomy of childhood and adulthood TS, we separately considered the sets of connections within each functional network and those between each pair of functional networks. We tested whether developmental stage (child, adult), diagnosis (TS, control), or an interaction between these factors was present among these connections. We found that developmental changes for most functional networks in TS were unaltered (i.e., developmental differences in TS were similar to those in typically developing children and adults). However, there were several within-network and cross-network connections that exhibited either “divergent” or “attenuated” development in TS. Connections involving the somatomotor, cingulo-opercular, auditory, dorsal attention, and default mode networks diverged from typical development in TS, demonstrating enhanced functional connectivity in adulthood TS. In contrast, connections involving the basal ganglia, thalamus, cerebellum, auditory, visual, reward, and ventral attention networks showed attenuated developmental differences in TS. These results suggest that adulthood TS is characterized by increased functional connectivity among functional networks that support cognitive control and attention, which may be implicated in suppressing, producing, and attending to tics. In contrast, subcortical systems that have been implicated in the initiation and production of tics may be immature in adulthood TS. Jointly, our results reveal how several cortical and subcortical functional networks interact and differ across development in TS.
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Removal of high frequency contamination from motion estimates in single-band fMRI saves data without biasing functional connectivity

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DOI: https://doi.org/10.1101/837161
Authors: Caterina Gratton In X Ally Dworetsky In X Rebecca Coalson In X Babatunde Adeyemo In X Timothy Laumann In X Gagan Wig In X Tania Kong In X Gabriele Gratton In X Monica Fabiani In X Deanna Barch In X Daniel Tranel In X Oscar Miranda-Dominguez In X Damien Fair In X Nico Dosenbach In X Abraham Snyder In X Joel Perlmutter In X Steven Petersen In X Meghan Campbell In X
Abstract: Denoising fMRI data requires assessment of frame-to-frame head motion and removal of the biases motion introduces. This is usually done through analysis of the parameters calculated during retrospective head motion correction (i.e., ‘motion’ parameters). However, it is increasingly recognized that respiration introduces factitious head motion via perturbations of the main (B0) field. This effect appears as higher-frequency fluctuations in the motion parameters (> 0.1 Hz, here referred to as ‘HF-motion’), primarily in the phase-encoding direction. This periodicity can sometimes be obscured in standard single-band fMRI (TR 2.0 – 2.5 s.) due to aliasing. Here we examined (1) how prevalent HF-motion effects are in seven single-band datasets with TR from 2.0 - 2.5 s and (2) how HF-motion affects functional connectivity. We demonstrate that HF-motion is relatively trait-like and more common in older adults, those with higher body mass index, and those with lower cardiorespiratory fitness. We propose a low-pass filtering approach to remove the contamination of high frequency effects from motion summary measures, such as framewise displacement (FD). We demonstrate that in most datasets this filtering approach saves a substantial amount of data from FD-based frame censoring, while at the same time reducing motion biases in functional connectivity measures. These findings suggest that filtering motion parameters is an effective way to improve the fidelity of head motion estimates, even in single band datasets. Particularly large data savings may accrue in datasets acquired in older and less fit participants.

Highlights

- Single-band fMRI motion traces show factitious high-frequency content ( HF-motion ) - The magnitude of HF-motion relates to age and other demographic factors - HF-motion elevates framewise displacement (FD) and causes data loss - Substantial fMRI data can be recovered from censoring by filtering motion traces - Filtering motion traces reduces motion artifacts in functional connectivity
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Atypical Functional Connectivity in Tourette Syndrome Differs Between Children and Adults

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DOI: https://doi.org/10.1101/459560
Authors: Ashley Nielsen In X Caterina Gratton In X Jessica Church In X Nico U.F. Dosenbach In X Kevin Black In X Steven Petersen In X Bradley Schlaggar In X Deanna Greene In X
Abstract:

ABSTRACT

Background

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics that typically change over development. Whether and how brain function in TS also differs across development has been largely understudied. Here, we used functional connectivity MRI to examine whole brain functional networks in children and adults with TS.

Methods

Multivariate classification methods were used to find patterns among functional connections that distinguish TS from controls separately for children and adults (total N = 202). We tested whether the patterns of connections that classify diagnosis in one age group (e.g., children) could classify diagnosis in another age group (e.g., adults). We also tested whether the developmental trajectory of these connections were altered in TS.

Results

Patterns of functional connections that distinguished TS from controls were generalizable to an age-matched independent test set, but not to other age groups. While diagnostic classification was successful in children and adults separately, the connections that best distinguished TS from controls were age-specific. When contextualized with typical development, some functional connections exhibited accelerated maturation in childhood TS, while others exhibited delayed maturation in adulthood TS.

Conclusions

Our results demonstrate that brain networks are differentially altered in children and adults with TS, and that the developmental trajectory of affected connections is disrupted. These findings further our understanding of neurodevelopmental trajectories in TS and carry implications for future applications aimed at predicting the clinical course of TS in individuals over development.
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A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum

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DOI: https://doi.org/10.1101/450452
Authors: Benjamin Seitzman In X Caterina Gratton In X Scott Marek In X Ryan Raut In X Nico U.F. Dosenbach In X Bradley Schlaggar In X Steven Petersen In X Deanna Greene In X
Abstract: An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011 and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels.
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Reward-related regions form a preferentially coupled system at rest

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DOI: https://doi.org/10.1101/304865
Authors: Jeremy Huckins In X Babatunde Adeyemo In X Fran Miezin In X Jonathan Power In X Evan Gordon In X Timothy Laumann In X Todd Heatherton In X Steven Petersen In X William Kelley In X
Abstract: Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence even in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc, anatomically defined) and orbitofrontal cortex (OFC, functionally defined) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Further, differences may exist in the pathways through which control systems interact with key regions of this reward system. Whereas NAcc regions of the reward system are functionally connected to cingulo-opercular and default systems, OFC regions of the reward system show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in the current work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.
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Correction of respiratory artifacts in MRI head motion estimates

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DOI: https://doi.org/10.1101/337360
Authors: Damien Fair In X Oscar Miranda-Dominguez In X Abraham Snyder In X Anders Perrone In X Eric Earl In X Andrew Van In X Jonathan Koller In X Eric Feczko In X Rachel Klein In X Amy Mirro In X Jacqueline Hampton In X Babatunde Adeyemo In X Timothy Laumann In X Caterina Gratton In X Deanna Greene In X Bradley Schlaggar In X Don Hagler In X Richard Watts In X Hugh Garavan In X Deanna Barch In X Joel Nigg In X Steven Petersen In X Anders Dale In X Sarah Feldstein-Ewing In X Bonnie Nagel In X Nico U.F. Dosenbach In X
Abstract: Head motion represents one of the greatest technical obstacles for brain MRI. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, this estimation may be corrupted by factitious effects owing to main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and a comparison ‘single-shot’ dataset from Oregon Health & Science University. We show unequivocally that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with degraded quality of functional MRI. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects. Subsequently, we demonstrate that utilizing this filter improves post-processing data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.
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